Introduction

Nesfatin-1, an 82 amino acid peptide first identified by Oh-l and his colleagues in 2006, was initially thought to inhibit food intake and to be a satiety factor [1]. Immunohistochemistry has shown that the nesfatin-1 precursor is a non-esterified fatty acid/nuclear binding protein 2 (NUCB2) and that nesfatin-1 is secreted in the pancreas, stomach and duodenum [2], as well as in various locations in the central nervous system such as the pituitary, hypothalamus and brainstem [3]. Nesfatin-2 and nesfatin-3 are also cleaved and processed from the precursor NUCB2, but their function is not yet known [1]. Nesfatin-1 has anorexic and anti-hyperglycemic effects, thus regulating food intake and energy homeostasis [4]. Studies have found that nesfatin-1 levels have predictive value in a variety of diseases and that modulating nesfatin-1 levels may be a potential target for disease treatment. For example, nesfatin-1 can improve myocardial ischaemia [5]and reduce the size of myocardial infarction [6]. Nesfatin-1 has important predictive value and is a potential therapeutic target in diseases such as glucose regulation, lipid metabolism and nervous system disorders [7,8,9].

Neurological diseases are characterized by complexity, diversity and difficulty in treatment and rehabilitation, which impose a huge burden on patients and their families [10]. With the continuous development of therapeutic techniques, new directions have been taken in the treatment of some neurological diseases, but in many cases there are still no effective treatments or drugs, and the search for and development of neuroprotective agents continues to be a topic of interest to researchers. At the same time, neurological recovery is slow, and for most diseases there are no very effective observables or markers of disease progression and prognosis. The high cost and harm of imaging tests and invasive tests also make follow-up review of patients difficult [11].

Nesfatin-1 is closely associated with neurological disorders, while nesfatin-1 can cross the blood-brain barrier in a non-saturated form and has disease predictive value. In animal studies, nesfatin-1 was also found to be effective in improving neurological symptoms by altering levels, and may be a therapeutic target for neurological disorders [12]. The aim of this review is to systematically describe the role of nesfatin-1 in neurological diseases. And nesfatin-1 may be a predictor and therapeutic target for clinically related diseases of the nervous system.

Methods

Search Strategy

A search was conducted for studies on nesfatin-1 and the nervous system in PubMed, CNKI and Baidu Scholar, with literature published from the time of database creation to January 2023, including Chinese literature and English literature. Literature searches were conducted using nesfatin or nesfatin-1 matched with the following search terms. Search terms include: (1) Nervous system; (2) Neurological diseases; (3) biomarkers; (4) Diseases of nervous system, such as Alzheimer’s disease(AD), Parkinson’s disease(PD), epilepsy and Subarachnoid hemorrhage(SAH).

The initial screening of the literature was based on the titles and abstracts of the articles; thereafter, a complete review of the literature was undertaken.

Inclusion and Exclusion Criteria

Our study is based on the role of nesfatin-1 as a marker in neurological diseases and on nesfatin-1 as a potential target for the treatment of neurological diseases. These studies illustrate the predictive role of nesfatin-1 in disease by analysing nesfatin-1 levels in samples such as blood from animals or clinical patients, and also illustrate nesfatin-1 as a therapeutic target in the nervous system by behavioural studies in in vivo models and pathophysiological analyses in in vitro models.

Based on the statistical classification and writing needs of the review, the following criteria were used to include and exclude literature for this review: (1) the literature was a study of the therapeutic effects of nesfatin-1 or a test of Nesfatin-1 levels; (2) the study had to have a control group; (3) the study had to be neurologically relevant.

The exclusion criteria for systematic review were as follows: (1) reviews; (2) studies in which nesfatin-1 was used in combination with other therapeutic agents; (3) studies without a control group.

Literature Screening and data Extraction

Two authors independently collected primary literature and resolved disputes through discussion. The following information was retrieved from each study:

  1. 1.

    Marker-based studies: (1) Type of disease; (2) Data source; (3) Sample size; (4) Sample source; (5) Nesfatin-1 levels; (6) Main conclusions; (7) References.

  2. 2.

    Therapeutic studies: (1) Type of disease; (2) Species or model used for studies; (3) Model-inducing drug used for studies; (4) Dose of nesfatin-1 or nesfatin-1 antibody used in the experiment; (5) Main results and mechanism of the study; (6) First author of the literature and year of publication.

Result

After initial screening, a total of 2663 articles were included, including 734 articles in Pubmed, 1009 articles in CNKI and 890 articles in Baidu Academic. Due to duplication between databases, a total of 42 articles were included after applying the above exclusion and inclusion criteria, followed by reading the abstracts to ultimately include a total of 26 articles (Fig. 1).

Fig. 1
figure 1

Study selection, inclusion and exclusion criteria

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Marker-based Studies

A total of 13 studies were included in the marker category, 11 studies reported human data and 2 were animal data. These studies included ischaemic stroke (n = 1), aneurysm, subarachnoid haemorrhage or cerebral haemorrhage (n = 4), PD (n = 1), AD (n = 2), epilepsy (n = 4), multiple sclerosis (n = 1). 11 human data studies included a total of 1113 individuals and data comparisons included healthy patients over the same period and comparisons of patients with different transitions. 10 of the 13 studies studied serum Nesfatin-1 levels, 1 studied plasma Nesfatin-1 levels and the other 2 studies studied serum and hypothalamic nesfatin-1 levels and serum and salivary nesfatin-1 levels respectively. (Table 1)

Table 1 nesfatin-1 marker-based studies
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Therapeutic Studies

The therapeutic studies consisted of 13 studies, including cerebral ischemia-reperfusion (n = 5), subarachnoid hemorrhage (n = 1), PD (n = 6), and epilepsy (n = 1). 9 of the 13 studies are in vivo experiments, 2 studies are in vitro experiments, and one is in vivo and in vitro experiment. Animal models for in vivo experiments included SD rats, Wistar rats, and C57BL/6 mice, while in vitro studies used MES23.5 cells (a dopaminergic neuroblastoma), dopamine neurons. 11 of the 13 studies used nesfatin-1 for expriment, and the other 2 studies used nesfatin-1 antibodies to explore the therapeutic target effectiveness of nesfatin-1 from a directional perspective. (Table 2)

Table 2 nesfatin-1 therapeutic research
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Discussion

Ischemic Stroke and Cerebral ischaemia-reperfusion

Stroke is one of the major life-threatening diseases and is also prone to significant sequelae, resulting in permanent disability [13]. Strokes include ischaemic strokes and haemorrhagic strokes, of which ischaemic strokes account for about 80% of cerebrovascular disease and cause severe neurological impairment; including impaired limb movement, hemiparesis and impaired consciousness [14]. Effective predictors can help in the prognosis and selection of treatment options.

In a study of 46 patients with acute stroke and a control group consisting of 32 healthy individuals, serum nesfatin-1 levels were found to be 295.8 ng/mL in the experimental group and 387.5 ng/mL in the control group, and serum nesfatin-1 levels were lower in patients with cerebral infarction than in healthy controls (p = 0.0282), but were not associated with stroke severity [15]. This study included a small sample size and more sample studies are needed to confirm the association between nesfatin-1 levels and ischaemic stroke.

With the development of thrombolytic and interventional therapies, ischemia-reperfusion injury has also received increasing attention from researchers [16]. Timely restoration of blood flow is an effective treatment for patients with acute ischaemic stroke, but restoration of blood supply can increase cellular damage to brain tissue [17]. The pathological changes may occur as a result of the interaction of mechanisms such as cell necrosis, inflammatory response, apoptosis and oxidative damage [18]. Neuronal necrosis in the ischemic core was found to be mostly irreversible, while apoptosis was found in the ischemic semidark zone [19]. Inflammation is one of the important steps in the development and progression of brain injury during ischemia [20, 21]. Astrocytes are the main cells of the central system that maintain normal physiological functions [22]. Activated aggregates of astrocytes can secrete large amounts of glial fibrillary acidic protein (GFAP) [23], so GFAP is often used as an indicator of neuroinflammation levels [24]. High GFAP levels correlate with the degree of neuronal damage and serum GFAP levels correlate positively with NIHSS scores [25]. Ionic calcium-binding bridging protein-1 (Iba-1) is another commonly used assay for glial cell activation. Iba-1 is an actin-binding protein that is specifically expressed in all microglia and also plays a role in regulating microglial cell function, particularly in activated microglia, so it is widely used as a marker of microglial cell activation [26]. Improving nesfatin-1 levels not only improved the behavioral memory impairment induced by cerebral ischemia-reperfusion in rats, but also reduced the level of Iba-1 protein. Wistar rats with clamped common carotid arteries had significantly increased GFAP and cell necrosis, whereas nesfatin-1-treated rats had decreased GFAP levels with attenuated inflammatory response by inhibition of astrocyte activation [27]. Erfani S et al. also conducted experiments using the Wistar rat animal model and found that nesfatin-1 was also able to reduce malondialdehyde (MDA) concentration and increased superoxide dismutase (SOD) and glutathione (GSH) levels [28]. As we know, oxidative stress damage plays a role in many aspects of neurological diseases, and oxidative stress damage occurs when the production of large amounts of free radicals exceeds the antioxidant limit [29]. The decrease in MDA levels represents an inhibition of oxidative damage and a reduction in lipid peroxidation by nesfatin-1 [30]. It also improves the progression of ischaemic stroke by increasing the levels of antioxidants such as SOD and GSH [28]. In addition, inhibition of neuronal apoptosis is an important pathway to reduce brain tissue damage [31], and the cysteine protease (Caspase) family dominates the apoptosis machinery [32]. The endogenous pathway is based on increasing the expression of the apoptotic protein BCL2-Associated X (Bax) and inhibiting the expression of the B-cell lymphoma-2 (Bcl-2) [33]. After applying a modified Zea-Longa wire bolus method to construct a model of cerebral ischemic reperfusion and treating rats with nesfatin-1, the researchers found a decrease in brain caspase-3 expression and an increase in the Bcl-2/Bax ratio indicating the inhibition of apoptotic protein expression [34]. This is consistent with the results observed by Erfani et al. [27, 35], while they both suggested that nesfatin-1 reduced the extent of lesion damage and the level of apoptosis in the hippocampal region. Nesfatin-1 not only inhibited apoptosis but also increased the expression levels of calmodulin-dependent kinase 2 (CAMK II) and postsynaptic density protein 95 (PSD95) [36]. CAMKII and PSD95 are distributed in cell membranes and cell junctions and are sensitive to ischemic changes. After ischemia occurs, a series of pathological changes occur that decrease their expression, causing synaptic dysfunction and resulting in impaired cognitive function [37, 38]. Increased expression of CAMKII and PSD95 indicated that nesfatin-1 is an important therapeutic target for stroke, capable of improving stroke symptoms and reducing reperfusion injury through multiple pathways.

In conclusion, serum nesfatin-1 levels are significantly decreased in patients with ischaemic stroke and may serve as a marker of cerebral infarction condition and prognosis. In ischemia-reperfusion-induced injury, exogenous supplementation of nesfatin-1 or increased expression of nesfatin-1 levels can improve stroke symptoms and prognosis through multiple pathways, suggesting a possible new target for stroke therapy.

Subarachnoid Haemorrhage

Subarachnoid haemorrhage (SAH) is a neurological emergency with a high mortality rate, usually caused by ruptured aneurysms or vascular malformations [39]. Various types of angiography such as DSA, MRA and CTA are currently used for the diagnosis and etiology of SAH [40]. However, the prognosis of the patient is often difficult to estimate and the prognosis of the patient determines whether a more aggressive treatment strategy is needed [40]. Analysis of blood from both SAH and cerebral haemorrhage patients showed higher levels of nesfatin-1 in the case group than in the healthy group [41]. Plasma nesfatin-1 levels at admission were positively correlated with NHISS score and hematoma volume (p < 0.01) and were independently associated with poor 90-day prognosis, early neurological deterioration and hematoma enlargement (p < 0.05) [42]. This suggests that nesfatin-1 may be a predictor of prognosis in patients with haemorrhagic stroke.Cakir et al. analysed serum nesfatin-1 in 48 patients with SAH and also found that nesfatin-1 increased with increasing severity of SAH [43]. More notably, serum nesfatin-1 levels were positively correlated with the size and number of aneurysms [44]. This may be of great help in the follow-up of patients with unruptured aneurysms or those who cannot be treated surgically, and therefore serum nesfatin-1 is a potential marker of future aneurysm regression.

On top of its marker role, nesfatin-1 also demonstrates a protective effect against bleeding disorders, showing potential as a therapeutic target for this purpose. Blood was injected into the rat cisterna to induce the SAH model, and the level of inflammation and oxidative damage in the rat brain were significantly increased [45]. Nesfatin-1 significantly improved the inflammatory response in SAH rats and inhibited caspase-3 and myeloperoxidase (MPO) expression. MPO, a response indicator of neutrophil infiltration, reflected the anti-inflammatory activity of nesfatin-1. Nesfatin-1 also increased the levels of antioxidant substances in vivo, including SOD and GSH, and decreased MDA and protein carbonyl content (PCC) levels, and nesfatin-1 improved the levels of lipid peroxidation and protein carbonylation in the nervous system. In addition, electron microscopy showed that nesfatin-1 was able to reduce endothelial damage and exert vasodilatory effects [45].

SAH and haemorrhagic stroke cause inflammation, apoptosis, oxidative stress and vasospasm. The blood that breaks out of the blood vessels causes an inflammatory response, and inflammatory factors such as IL-6, TNF-α and CRP pass through the damaged blood-brain barrier and contribute to the increased expression of nesfatin-1, which is involved in the inflammatory response of the body [46]. It has also been suggested that increased levels of nesfatin-1 may be responsible for vasoconstriction, which is a defense mechanism of the system against aneurysms or irritants that cause rupture of the vascular system [47].

In conclusion, nesfatin-1 is predictive of disease regression in cerebral haemorrhage and SAH, and has implications for disease prognosis and treatment at different stages. Also nesfatin-1 exerts anti-inflammatory, antioxidant and edema-reducing effects as a therapeutic target in a subarachnoid haemorrhage disease model.

Parkinson’s Disease

PD is a major neurodegenerative disorder with progressive bradykinesia, resting tremor and postural gait disturbances as the main clinical manifestations [48]. PD gets its main pathological features as dopaminergic neuronal degeneration and the formation of Lewy bodies (eosinophilic inclusion bodies), which leads to dopaminergic neuronal degeneration and metabolic abnormalities, producing disease symptoms [49]. The pathogenesis of PD has not been universally agreed upon, but it is currently believed that the development of PD is associated with neuroinflammation, apoptosis, and mitochondrial dysfunction [48]. Therapeutic agents include dopamine supplements and dopamine agonists, but existing therapeutic agents only improve symptoms and their efficacy often decreases with time on medication [50]. Simple and accurate markers are important for PD disease progression and drug modification, while the active discovery of new therapeutic targets may help in the treatment of PD.

In a clinical trial that included 80 investigators, serum nesfatin-1 levels were 27.29 ± 11.07 pg/ml in PD patients and 100.49 ± 24.07 pg/ml in healthy controls, and serum nesfatin-1 levels were significantly lower in PD patients than in normal controls (p < 0.001) [51]. This corresponds to nesfatin-1 antibody-treated mice producing pathological changes in PD, and low levels of nesfatin-1 may be one of the initiating causes of PD pathogenesis, or PD pathogenesis leads to a significant depletion of nesfatin-1 in the body, thus exacerbating PD progression.

There are 6 articles about the effect of nesfatin-1 or nesfatin-1 antibody on Parkinson’s model in vivo and in vitro, including 2 in vitro experiments, 2 in vivo experiments and 2 in vivo and in vitro experiments. Shen et al. used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and :1-methyl-4-phenyl-pyridinium ion (MPP+) to induce C57BL/6 mice and MES23.5 cells, respectively, to simulate a PD model. The administration of the toxic inducer caused PD symptoms in mice, along with damage to dopaminergic neurons. In contrast, the cellular model showed decreased activity and mitochondrial dysfunction. After intervention with nesfatin-1, nesfatin-1 antagonized the decrease in dopamine, dopamine metabolite dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) levels caused by MPTP, and increased the number of TH-immunopositive cells in the SN region, TH protein expression, and TH-immunopositive nerve fiber endings in the Str region. Decreased numbers of TH-positive cells and nerve fibres suggest loss of dopamine neurons [52]. Dopaminergic neurons have a high energy requirement and mitochondrial disorders lead to dysregulation of energy metabolism resulting in neuronal damage, and in the case of extensive mitochondrial disorders, apoptosis of Iniqi neurons, which affects the normal physiological activity of neurons [53]. Mitochondrial disorders also increase the production of reactive oxygen species (ROS), and large amounts of ROS alter the permeability of the inner mitochondrial membrane, leading to a decrease in mitochondrial membrane potential [54]. The damaged mitochondria release cytochrome C (CytC) into the cytoplasm, and the release of CytC activates caspase-3, which exacerbates neuronal apoptosis [55]. nesfatin-1 exerts a dopaminergic protective effect through anti-apoptotic and improved mitochondrial function [56]. Shen et al. used the same PD model to explore the protective effects of nesfatin-1 on dopaminergic neurons. Nesfatin-1 improved dopamine and its metabolite levels and reduced TH neuronal loss, and it was able to promote C-Raf-ERK1/2 signaling pathway expression based on protection of mitochondria and inhibition of caspase-3 activation [57]. C-Raf and ERK1/2 are associated with cell survival and are involved in the regulation of apoptosis [58]. To verify whether C-Raf and ERK1/2 are involved in the neuroprotective effects of nesfatin-1, Shen et al. used the specific inhibitors of C-Raf and ERK1/2, GW5074 and PD98059, respectively. nesfatin-1 was unable to effectively restore mitochondrial function and inhibit apoptosis after using the inhibitors. This suggests that nesfatin-1 antagonizes MPP+-induced neurotoxicity by activating the C-Raf-ERK1/2 signaling pathway [57]. Mitochondrial disorders are increasingly associated with the development of PD, and the interaction of mitochondrial respiratory chain complex I dysfunction, free radical production, inflammation and apoptosis caused by mitochondrial disorders accelerates the progression of PD [59]. Mitochondrial respiratory chain complex I dysfunction accelerates ROS production and ATP consumption, creating a cascade of reactions that accelerate neuronal damage [60]. Gastrodia can readily enter cells through its high lipid solubility and then specifically inhibit mitochondrial respiratory chain complex I, leading to mitochondrial dysfunction [61], inducing degeneration of the nigrostriatal pathway and ultimately cause pathological changes similar to PD [62]. Similar findings of anti-apoptotic and protective mitochondrial function were found in rotenone-induced MES23.5 cells, while the inhibitory effect of nesfatin-1 on ROS production was clarified [63]. Dopaminergic neuronal electrophysiological abnormalities are responsible for the susceptibility to PD [64], and excitotoxic or hypoactive effects may lead to dopamine neuron death [65]. The possible neuroprotective effects of nesfatin-1 through inhibition of neuronal excitability have received attention [66]. Nesfatin-1 is able to reduce the excitability of nigrostriatal dopaminergic neurons and exert a signaling modulating effect on postsynaptic inhibition [67]. The exogenous use of nesfatin-1 initially demonstrated a therapeutic effect on PD, and the use of nesfatin-1 antibodies to reduce nesfatin-1 levels in animal models to investigate the presence of PD symptoms and pathological changes further validated the neuroprotective effects of nesfatin-1. In C57BL/6 mice injected with nesfatin-1 antibody, a decrease in TH-immunopositive cells and nerve terminal fibers was observed, along with a decrease in dopamine and its metabolites. Nesfatin-1 antibody promoted caspase-1 activity and induced neuronal apoptosis. Notably, nesfatin-1 antibodies reduced the length of the number of mitochondria in the nervous system, which may be responsible for mitochondrial dysfunction [68]. Chen et al. came to similar conclusions, while they also observed that nesfatin-1 antibodies promoted 1/2ERK expression and upregulated brain-derived neurotrophic factor (BDNF) expression [69]. BDNF, a neurotrophic factor, exerts anti-apoptotic and antioxidant effects, and nesfatin-1 antibodies reduced the number of dopamine neurons, and the increase in BDNF may be a compensatory response that initiates a protective program [69].

Treatment with nesfatin-1 and nesfatin-1 antibodies illustrates nesfatin-1 as a therapeutic targettheir with protective effects on the dopaminergic nervous system, while low levels of nesfatin-1 may be used as an indicator for early diagnosis of PD or evaluation of treatment efficacy.

Alzheimer’s Disease

AD is an important neurodegenerative disease and a major cause of dementia [70]. Aβ amyloid deposition, protein misfolding, and neuroinflammation are thought to be the main mechanisms of AD development. However, the sensitivity of existing imaging tests to amyloid deposition and abnormal protein entanglement is low, and a true diagnosis of AD is only possible through autopsy. Detection of Aβ1–42 or tau protein in the cerebrospinal fluid is thought to be of interest in the diagnosis of AD [71]. However, lumbar puncture is an invasive test that is not suitable for long-term follow-up and outpatient practice, so it is essential to find non-invasive biomarkers with high sensitivity and specificity. In animal studies, STZ injection into the hippocampus induced behavioral impairment in a mouse model of AD, and the mice exhibited learning memory deficits [72]. The serum concentration of nesfatin-1 was significantly increased in mice with bilateral hippocampal STZ injection compared to control mice (p < 0.01) [73]. In a trial that included 39 patients with AD, serum nesfatin-1 levels were 200.4 ± 191.7 pg/ml in the case group compared to 113.5 ± 145.8 pg/ml in the healthy control group during the same period. 0.001) [74]. Both animal and clinical studies suggest elevated levels of nesfatin-1 in AD patients, and in the previous study we discussed that nesfatin-1 has anti-inflammatory, antioxidant and anti-apoptotic neuroprotective effects, which may explain why serum nesfatin-1 levels are higher in AD than in control subjects.

Epilepsy

Epilepsy is a common neurological disorder characterized by brain dysfunction caused by abnormal neuronal discharges [75], and its clinical manifestations are mainly convulsive seizures, impaired consciousness and myoclonus [76].

The EEG is a common adjunct to the diagnosis of epilepsy. In some cases, however, the EEG is normal, no abnormal EEGs are produced during the monitoring interval, or the EEG abnormalities are not obvious, which makes diagnosis difficult [77]. At the same time, current medication can only reduce the frequency of seizures, while surgery is more expensive and its effectiveness is uncertain [78]. The lack of validated, easily accessible biochemical markers is one of the difficulties in the follow-up of patients with epilepsy, as the dose or type of medication often needs to be adjusted during the long-term treatment of epilepsy. It is important to look for therapeutic drugs and markers for diagnosis and follow-up of the condition. Elevated levels of nesfatin-1 were observed in 1 animal study and 3 human studies. In animal studies, a decrease in serum and hypothalamic nesfatin-1 was observed following the use of antiepileptic drugs, but the levels were still higher than in the blank control group [79]. Aydin et al. obtained similar findings in human serum and saliva, with pre-treatment serum nesfatin-1 levels of 25.8 ± 5.84 ng/ml and salivary nesfatin-1 levels of 33.5 ± 8.79 ng/ml in patients with epilepsy. Serum nesfatin-1 levels decreased approximately 8-fold and salivary nesfatin-1 levels decreased 10-fold after the use of antiepileptic drugs, but were still higher than in controls. In another study of 70 patients with epilepsy with long-term follow-up, 22 of the 70 patients died and serum nesfatin-1 levels were higher in the death group than in the survival group, with statistically significant differences in levels. It can be assumed that there is a positive correlation between the severity of the epilepsy patients [80]. This is highly suggestive of changes in the patient’s condition, and the timely detection of exacerbations may allow for consideration of more aggressive treatment to improve the patient’s prognosis. In addition, serum nesfatin-1 levels were measured at 5 min, 1 and 5 h after the seizure and were found to be significantly higher [81]. This may provide a new diagnostic basis for patients with negative EEG results, or for patients with recent seizures. The mechanism of elevated levels of nesafatin-1 in patients with epilepsy was unknown, but previous studies have reported that nesfatin-1 stimulated depolarization of PVN neurons. Excessive release of nesfatin-1 may lead to excitotoxicity, which may be associated with epilepsy [82].

Valproic acid, carbamazepine and diazepam are still commonly used for the treatment of grand mal seizures, focal seizures and persistent epilepsy.Some neurotrophic drugs also cause neuronal electrical activity that can trigger seizures. The hypoxia and neurological damage caused by seizures often requires a period of neurological recovery. Nesfatin-1 has the potential to be a new target for epilepsy. In animal studies, nesfatin-1 was used in the pentylenetetrazol-induced epilepsy model of the Wistar albino rat, and after treatment with nesfatin-1, it was observed that nesfatin-1 alleviated pentylenetetrazol-induced seizures, and pathological damage to neurons in the hippocampus was alleviated. Further immunohistochemical assays showed that nesfatin-1 increased GSH levels and decreased MDA levels, protecting against epilepsy-induced neurological damage in an anti-oxidative stress manner, while nesfatin-1 was able to maintain GFAP activity and exert anti-inflammatory effects [83].

It is not clear whether epilepsy causes an increase in nesfatin-1 secretion or whether nesfatin-1 induces epilepsy. However, nesfatin-1 as an epilepsy therapeutic target is gradually being demonstrated, and its use as a marker for epilepsy diagnosis, diagnosis and follow-up has been progressively confirmed, and more sample and multicentre studies are needed to further clarify the potential of nesfatin-1 as an epilepsy marker.

Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by spatial and temporal multiplicity [84]. In addition to the imaging signs, positive cerebrospinal fluid and serum IgG oligoclonal bands mostly support the diagnosis of MS. The alteration of nesfatin-1 in the serum of MS patients can avoid the physical and financial burden of multiple lumbar punctures and MRI [85]. Serum nesfatin-1 levels were lower in MS patients than in controls and the critical value of nestatin-1 was 7.155 ng/mL with a sensitivity of 0.682 and specificity of 0.643. Reduced levels of nesfatin-1 may contribute to MS pathogenesis, such as inflammation, oxidative stress and apoptosis in MS, leading to demyelination, axonal damage with neuronal loss and gliosis. Nesfatin-1 is expected to be a biomarker for the diagnosis of MS and to assess the response to treatment in the course of MS [86].

Conclusion

This review includes 13 marker properties studies and 13 therapeutic studies of nesfatin-1, and draws the following conclusions. Nesfatin-1 levels were higher in patients with SAH and cerebral haemorrhage than in the healthy group, and correlated positively with severity of disease and haematoma volume. Serum nesfatin-1 levels were positively correlated with the size and number of aneurysms. In neurodegenerative diseases, nesfatin-1 levels were lower in PD patients than in healthy controls, and higher in AD patients than in healthy controls. This may be related to the fact that patients are at different stages of the disease and at different sites of lesion, and needs to be further explored. Elevated serum nesfatin-1 levels in patients with epilepsy have a positive correlation between the condition and the severity of the disease. With further research, the feasibility of nesfatin-1 as a marker for neurological disorders can be further established, improving the sensitivity and specificity of diagnosis, reducing the financial and physical burden of imaging and invasive procedures during follow-up, and indicating the evolution of disease progression, leading to timely adjustment of treatment and improved patient prognosis. Nesfatin-1 has the ability to be a marker while nesfatin-1 also has the potential to be a neurological therapeutic target, and by modulating nesfatin-1 expression or in vivo levels it is possible to induce anti-inflammatory, antioxidant, anti-apoptotic and mitochondrial protective effects that can alleviate or treat various neurological disorders (Fig. 2).

Fig. 2
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Nesfatin-1 neuroprotective mechanism

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In conclusion, nesfatin-1 is a potential marker for neurological diseases and may become a new target for the treatment of neurological diseases.