Summary.
The neuroprotective effect of the antiparkinsonian monoamine oxidase (MAO)-B inhibitor, R-(−)-deprenyl has been under investigation for years. Cytoskeleton, a main component of cell adhesion, is involved in the development of R-(−)-deprenyl-responsive diseases, the effect of the drug on cell adhesion, however, is not known. We examined the effect of R-(−)-deprenyl on cell–cell adhesion of neuronal and non-neuronal cells. R-(−)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell–cell adhesion of PC12 and NIH3T3 cells at concentrations lower than those required for MAO-B inhibition, while S-(+)-deprenyl was not effective. This acitvity of R-(−)-deprenyl was not prevented by the cytochrome P-450 inhibitor, SKF525A, while deprenyl-N-oxide, a newly described metabolite, also induced an increase in cell–cell adhesion. The effect of R-(−)-deprenyl was not reversible during a 24-hour recovery period. In summary, we described a new, MAO-B independent effect of R-(−)-deprenyl on cell–cell adhesion which can contribute to its neuroprotective function.
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S Abu-Raya R Tabakman E Blaugrund V Trembovler P Lazarovici (2002) ArticleTitleNeuroprotective and neurotoxic effects of monoamine oxidase-B inhibitors and derived metabolites under ischemia in PC12 cells. Eur J Pharmacol 434 109–116 Occurrence Handle10.1016/S0014-2999(01)01548-5 Occurrence Handle11779573
H Braak E Braak (2000) ArticleTitlePathoanatomy of Parkinson’s disease. J Neurol 247 II/3–II/10
MC Carrillo S Kanai M Nokubo K Kitani (1991) ArticleTitle(−) Deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. Life Sci 48 517–521 Occurrence Handle10.1016/0024-3205(91)90466-O Occurrence Handle1899460
P Coleman H Federoff R Kurlan (2004) ArticleTitleA focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology 63 1155–1162 Occurrence Handle15477531
A Falsaperla PA Monici Preti C Oliani (1990) ArticleTitleSelegiline versus oxiracetam in patients with Alzheimer-type dementia. Clin Ther 12 376–384 Occurrence Handle2125242
V Filip E Kolibas (1999) ArticleTitleSelegiline in the treatment of Alzheimer’s disease: a long-term randomized placebo-controlled trial. Czech and Slovak Senile Dementia of Alzheimer Type Study Group. J Psychiatry Neurosci 24 234–243 Occurrence Handle10354658
CC Garner RG Zhai D Gundelfinger NE Ziv (2002) ArticleTitleMolecular mechanisms of CNS synaptogenesis. Trends Neurosci 25 243–250 Occurrence Handle10.1016/S0166-2236(02)02152-5 Occurrence Handle11972960
EA Grace J Busciglio (2003) ArticleTitleAberrant activation of focal adhesion proteins mediates fibrillar amyloid beta-induced neuronal dystrophy. J Neurosci 23 493–502 Occurrence Handle12533609
M Hamada-Kanazawa K Ishikawa K Nomoto T Uozumi Y Kawai M Narahara M Miyake (2004) ArticleTitleSox6 overexpression causes cellular aggregation and the neuronal differentiation of P19 embryonic carcinoma cells in the absence of retinoic acid. FEBS Lett 560 192–198 Occurrence Handle10.1016/S0014-5793(04)00086-9 Occurrence Handle14988021
GU Höglinger P Rizk MP Muriel C Duyckaerts WH Oertel I Caille EC Hirsch (2004) ArticleTitleDopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 7 726–735 Occurrence Handle10.1038/nn1265 Occurrence Handle15195095
K Jin AL Peel XO Mao L Xie BA Cottrell DC Henshall DA Greenberg (2004) ArticleTitleIncreased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci USA 101 343–347 Occurrence Handle10.1073/pnas.2634794100 Occurrence Handle14660786
E Junn MM Mouradian (2002) ArticleTitleHuman alpha-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci Lett 320 146–150 Occurrence Handle10.1016/S0304-3940(02)00016-2 Occurrence Handle11852183
M Katagi M Tatsuno A Miki M Nishikawa K Nakajima H Tsuchihashi (2001) ArticleTitleSimultaneous determination of selegiline N-oxide, a new indicator for selegiline administration, and other metabolites in urine by high-performance liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr B Biomed Sci Appl 759 125–133 Occurrence Handle10.1016/S0378-4347(01)00213-4 Occurrence Handle11499616
M Katagi M Tatsuno H Tsutsumi A Miki T Kamata H Nishioka K Nakajima M Nishikawa H Tsuchihashi (2002) ArticleTitleUrinary excretion of selegiline-N-oxide, a new indicator for selegiline administration in man. Xenobiotica 32 823–831 Occurrence Handle10.1080/00498250210144857 Occurrence Handle12396278
D Kiryushko T Kofoed G Skladchikova A Holm V Berezin E Bock (2003) ArticleTitleA synthetic peptide ligand of neural cell adhesion molecule, (NCAM), C3d, promotes neuritogenesis and synaptogenesis and modulates presynaptic function in primary cultures of rat hippocampal neurons. J Biol Chem 278 12325–12334 Occurrence Handle10.1074/jbc.M211628200 Occurrence Handle12502709
J Knoll (1993) ArticleTitleThe pharmacological basis of the beneficial effects of (−)deprenyl (selegiline) in Parkinson’s and Alzheimer’s diseases. J Neural Transm [Suppl] 40 69–91
J Knoll Z Ecseri K Kelemen J Nivel B Knoll (1965) ArticleTitlePhenylisopropylmethyl-propinylamine (E-250), a new spectrum psychic energizer. Arch Int Pharmacodyn Ther 155 154–164 Occurrence Handle4378644
J Knoll K Magyar (1972) ArticleTitleSome puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 5 393–408 Occurrence Handle5066229
E Koutsilieri JF O’Callaghan TS Chen P Riederer WD Rausch (1994) ArticleTitleSelegiline enhances survival and neurite outgrowth of MPP(+)-treated dopaminergic neurons. Eur J Pharmacol 269 R3–R4 Occurrence Handle10.1016/0922-4106(94)90048-5 Occurrence Handle7895766
I Laplante R Beliveau J Paquin (2004) ArticleTitleRhoA/ROCK and Cdc42 regulate cell–cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells. J Neurobiol 60 289–307 Occurrence Handle10.1002/neu.20036 Occurrence Handle15281068
SJ Lee K Drabik NJ Van Wagoner S Lee C Choi Y Dong EN Benveniste (2000) ArticleTitleICAM-1-induced expression of proinflammatory cytokines in astrocytes: involvement of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways. J Immunol 165 4658–4666 Occurrence Handle11035109
K Magyar B Szende (2004) ArticleTitle(−)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and antiapoptotic properties. Neurotoxicol 25 233–242 Occurrence Handle10.1016/S0161-813X(03)00102-5
K Magyar B Szende J Lengyel K Tekes (1996) ArticleTitleThe pharmacology of B-type selective monoamine oxidase inhibitors; milestones in (−)-deprenyl research. J Neural Transm [Suppl] 48 29–43
K Magyar M Pálfi T Tábi H Kalász B Szende Szökő É (2004) ArticleTitlePharmacological aspects of (−)-deprenyl. Curr Med Chem 11 2017–2031 Occurrence Handle15279565
M Mikkonen H Soininen T Tapiola I Alafuzoff R Miettinen (1999) ArticleTitleHippocampal plasticity in Alzheimer’s disease: changes in highly polysialylated NCAM immunoreactivity in the hippocampal formation. Eur J Neurosci 11 1754–1764 Occurrence Handle10.1046/j.1460-9568.1999.00593.x Occurrence Handle10215928
RB Postuma W He J Nunan K Beyreuther CL Masters CJ Barrow DH Small (2000) ArticleTitleSubstrate-bound beta-amyloid peptides inhibit cell adhesion and neurite outgrowth in primary neuronal cultures. J Neurochem 74 1122–1130 Occurrence Handle10693944
F Qin J Shite W Mao CS Liang (2003) ArticleTitleSelegiline attenuates cardiac oxidative stress and apoptosis in heart failure: association with improvement of cardiac function. Eur J Pharmacol 461 149–158 Occurrence Handle10.1016/S0014-2999(03)01306-2 Occurrence Handle12586210
EE Sander JP Klooster S van Delft RA van Kammen JG Collard (1999) ArticleTitleRac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behaviour. J Cell Biol 147 1009–1021 Occurrence Handle10.1083/jcb.147.5.1009 Occurrence Handle10579721
K Schlett A Czirók K Tárnok T Vicsek E Madarász (2000) ArticleTitleDynamics of cell aggregation during in vitro neurogenesis by immortalized neuroectodermal progenitors. J Neurosci Res 60 184–194
AL Schwarzman N Singh M Tsiper L Gregori A Dranovsky MP Vitek CG Glabe PH St George-Hyslop D Goldgaber (1999) ArticleTitleEndogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix. Proc Natl Acad Sci USA 96 7932–7937 Occurrence Handle10.1073/pnas.96.14.7932 Occurrence Handle10393925
BS Shankaranarayana Rao MK Lakshmana BL Meti TR Raju (1999) ArticleTitleChronic (−) deprenyl administration alters dendritic morphology of layer III pyramidal neurons in the prefrontal cortex of adult Bonnett monkeys. Brain Re 821 218–223 Occurrence Handle10.1016/S0006-8993(98)01362-6
HS Shin (1997) ArticleTitleMetabolism of selegiline in humans. Identification, excretion and stereochemistry of urine metabolites. Drug Metab Dispos 25 657–662 Occurrence Handle9193866
J Sivenius T Sarasoja H Aaltonen E Heinonen O Kilkku K Reinikainen (2001) ArticleTitleSelegiline treatment facilitates recovery after stroke. Neurorehabil Neural Repair 15 183–190 Occurrence Handle11944739
MG Spillantini RA Crowther R Jakes M Hasegawa M Goedert (1998) ArticleTitlealpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95 6469–6473 Occurrence Handle10.1073/pnas.95.11.6469 Occurrence Handle9600990
B Szende J Bökönyi J Bocsi Gy Kéri F Timár K Magyar (2001) ArticleTitleAnti-apoptotic and apoptotic action of (−)-deprenyl and its metabolites. J Neural Transm 108 25–33 Occurrence Handle10.1007/s007020170094 Occurrence Handle11261744
T Tábi K Magyar Szökő É (2003) ArticleTitleChiral characterization of deprenyl-N-oxide and other deprenyl metabolites by capillary electrophoresis using a dual cyclodextrin system in rat urine. Electrophoresis 24 2665–2673 Occurrence Handle10.1002/elps.200305468 Occurrence Handle12900880
BJ Tabner S Turnbull OM El-Agnaf D Allsop (2002) ArticleTitleFormation of hydrogen peroxide and hydroxyl radicals from A (beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer’s disease and Parkinson’s disease. Free Radic Biol Med 32 1076–1083 Occurrence Handle10.1016/S0891-5849(02)00801-8 Occurrence Handle12031892
WG Tatton WY Ju DP Holland C Tai M Kwan (1994) ArticleTitle(−)-Deprenyl reduces PC12 cell apoptosis by inducing new protein synthesis. J Neurochem 63 1572–1575 Occurrence Handle7931312
WG Tatton JS Wadia WY Ju RM Chalmers-Redman NA Tatton (1996) ArticleTitle(−)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase. J Neural Transm [Suppl] 48 45–59
WG Tatton RME Chalmers-Redman WY Ju J Waida NA Tatton (1997) ArticleTitleApoptosis in neurodegenerative disorders: potential for therapy by modifying gene transcription. J Neural Transm [Suppl] 49 245–268
WG Tatton RME Chalmers-Redman WJH Ju M Mammen GW Carlile AW Pong NA Tatton (2002) ArticleTitlePropargylamines induce antiapoptotic new protein synthesis in serum- and nerve growth factor (NGF)-withdrawn, NGF-differentiated PC-12 cells. J Pharmacol Exp Ther 301 753–764 Occurrence Handle10.1124/jpet.301.2.753 Occurrence Handle11961082
T Thomas C McLendon G Thomas (1998) ArticleTitleL-deprenyl: nitric oxide production and dilation of cerebral blood vessels. Neuroreport 9 2595–2600 Occurrence Handle9721939
T Thomas BR Bhavnani P Thomas (2002) ArticleTitleInhibition of human LDL oxidation by the neuroprotective drug l-deprenyl. Neurol Res 24 169–173 Occurrence Handle10.1179/016164102101199729 Occurrence Handle11877901
S Thyaga Rajan J Meites SK Quadri (1995) ArticleTitleDeprenyl reinitiates estrous cycles, reduces serum prolactin and decreases the incidence of mammary and pituitary tumors in old acyclic rats. Endocrinology 136 1103–1110 Occurrence Handle10.1210/en.136.3.1103 Occurrence Handle7867565
S Thyaga Rajan KS Madden SY Stevens DL Felten (1999) ArticleTitleInhibition of tumor growth by L-deprenyl involves neural-immune interactions in rats with spontaneously developing mammary tumors. Anticancer Res 19 5023–5028 Occurrence Handle10697505
S Thyaga Rajan KS Madden SY Stevens DL Felten (2000) ArticleTitleAnti-tumor effect of L-deprenyl is associated with enhanced central and peripheral neurotransmission and immune reactivity in rats with carcinogen-induced mammary tumors. J Neuroimmunol 109 95–104 Occurrence Handle10.1016/S0165-5728(00)00305-2 Occurrence Handle10996211
O Weinreb O Bar-Am T Amit O Chillag-Talmor MB Youdim (2004) ArticleTitleNeuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members. FASEB J 18 1471–1473 Occurrence Handle15247150
C Wersinger D Prou P Vernier A Sidhu (2003) ArticleTitleModulation of dopamine transporter function by alpha-synuclein is altered by impairment of cell adhesion and by induction of oxidative stress. FASEB J 17 2151–2153 Occurrence Handle12958153
C Wersinger P Vernier A Sidhu (2004) ArticleTitleTrypsin disrupts the trafficking of the human dopamine transporter by alpha-synuclein and its A30P mutant. Biochemistry 43 1242–1253 Occurrence Handle10.1021/bi035308s Occurrence Handle14756560
R-F Wu Y Ichikawa (1995) ArticleTitleInhibition of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolic activity of porcine FAD-containing monooxygenase by selective monoamine oxidase-B inhibitors. FEBS Lett 358 145–148 Occurrence Handle10.1016/0014-5793(94)01412-T Occurrence Handle7828725
PM Yip C Siu (2001) ArticleTitlePC12 cell utilize the homophilic binding site of L1 for cell–cell adhesion but L1-αvβ3 interaction for neurite outgrowth. J Neurochem 76 1552–1564 Occurrence Handle10.1046/j.1471-4159.2001.00152.x Occurrence Handle11238739
MB Youdim E Heldman HB Pollard P Fleming E McHugh (1986) ArticleTitleContrasting monoamine oxidase activity and tyramine induced catecholamine release in PC12 and chromaffin cells. Neuroscience 19 1311–1318 Occurrence Handle10.1016/0306-4522(86)90145-4 Occurrence Handle3822124
M Zhao S Momma K Delfani M Carlen RM Cassidy CB Johansson H Brismar O Shupliakov J Frisen AM Janson (2003) ArticleTitleEvidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci USA 100 7925–7930 Occurrence Handle10.1073/pnas.1131955100 Occurrence Handle12792021
J Zhu RJ Hamm TM Reeves JT Povlishock LL Phillips (2000) ArticleTitlePostinjury administration of L-deprenyl improves cognitive function and enhances neuroplasticity after traumatic brain injury. Exp Neurol 166 136–152 Occurrence Handle10.1006/exnr.2000.7484 Occurrence Handle11031090
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Jenei, V., Zor, K., Magyar, K. et al. Increased cell–cell adhesion, a novel effect of R-(−)-deprenyl. J Neural Transm 112, 1433–1445 (2005). https://doi.org/10.1007/s00702-005-0295-3
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DOI: https://doi.org/10.1007/s00702-005-0295-3