Pathogenesis of Parkinson's disease - prospects of neuroprotective and restorative therapies

被引:85
作者
Fernandez-Espejo, E [1 ]
机构
[1] Univ Seville, Dept Fisiol Med & Biofis, E-41009 Seville, Spain
关键词
6-OHDA; Parkinson disease; GDNF; TGF-beta(1); trophic factors;
D O I
10.1385/MN:29:1:15
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons of substantia nigra projecting to striatum. The cause of idiopathic PD is obscure, and most cases are sporadic. It is widely accepted that there is a genetic component of the disease, and the earlier the age of onset, the greater the likelihood that genetic factors play a dominant role. Oxidative stress of the substantia nigra seems to contain the driving force for neurodegeneration, leading to a destructive "toxic cycle." The most prevalent therapy is levodopa administration, but it is not efficacious after several years of treatment. Several alternative therapies are currently being explored, such as neuroprotective approaches. Compounds with potentially neuroprotective efficacy such as selegiline, dopamine agonists, riluzole, creatine, and coenzyme Q10 are currently being tested. Trophic factors represent another class of neuroprotective compounds, but their intracerebral administration is difficult to achieve. hi this respect, a potentially useful therapeutic approach is grafting cell vectors that release trophic molecules that stimulate regeneration in the damaged nigrostriatal system. Promising results have been obtained with fibroblasts engineered to secrete glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) or viral vectors expressing GDNF. We have tested the suitability of intrastriatal grafts of chromaffin cells obtained from the Zuckerkandl's organ, which exert beneficial effects in parkinsonian rats, and release trophic factors such as GDNF and transforming growth factor-beta(1) (TGF- beta(1)).
引用
收藏
页码:15 / 30
页数:16
相关论文
共 93 条
[1]   PRENATAL AND POSTNATAL-DEVELOPMENT OF RAT RETROPERITONEAL PARAGANGLIA [J].
AHONEN, M ;
SOINILA, S ;
JOH, TH .
JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM, 1987, 18 (02) :111-120
[2]   Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra [J].
Alam, ZI ;
Jenner, A ;
Daniel, SE ;
Lees, AJ ;
Cairns, N ;
Marsden, CD ;
Jenner, P ;
Halliwell, B .
JOURNAL OF NEUROCHEMISTRY, 1997, 69 (03) :1196-1203
[3]  
[Anonymous], 1996, Ann Neurol, V39, P29
[4]   Neuroprotective effect of riluzole in MPTP-treated mice [J].
Araki, T ;
Kumagai, T ;
Tanaka, K ;
Matsubara, M ;
Kato, H ;
Itoyama, Y ;
Imai, Y .
BRAIN RESEARCH, 2001, 918 (1-2) :176-181
[5]   Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged [J].
Beal, MF ;
Matthews, RT ;
Tieleman, A ;
Shults, CW .
BRAIN RESEARCH, 1998, 783 (01) :109-114
[6]   MESENCEPHALIC DOPAMINERGIC-NEURONS PROTECTED BY GDNF FROM AXOTOMY-INDUCED DEGENERATION IN THE ADULT BRAIN [J].
BECK, KD ;
VALVERDE, J ;
ALEXI, T ;
POULSEN, K ;
MOFFAT, B ;
VANDLEN, RA ;
ROSENTHAL, A ;
HEFTI, F .
NATURE, 1995, 373 (6512) :339-341
[7]   APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE [J].
BECKMAN, JS ;
BECKMAN, TW ;
CHEN, J ;
MARSHALL, PA ;
FREEMAN, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) :1620-1624
[8]   RE-INNERVATION OF THE DENERVATED STRIATUM BY SUBSTANTIA NIGRA TRANSPLANTS - FUNCTIONAL CONSEQUENCES AS REVEALED BY PHARMACOLOGICAL AND SENSORIMOTOR TESTING [J].
BJORKLUND, A ;
DUNNETT, SB ;
STENEVI, U ;
LEWIS, ME ;
IVERSEN, SD .
BRAIN RESEARCH, 1980, 199 (02) :307-333
[9]   ADRENAL-MEDULLA GRAFTS ENHANCE RECOVERY OF STRIATAL DOPAMINERGIC FIBERS [J].
BOHN, MC ;
CUPIT, L ;
MARCIANO, F ;
GASH, DM .
SCIENCE, 1987, 237 (4817) :913-916
[10]   EXPRESSION OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE IN RAT SYMPATHETIC-GANGLIA AND EXTRA-ADRENAL CHROMAFFIN TISSUE [J].
BOHN, MC ;
GOLDSTEIN, M ;
BLACK, IB .
DEVELOPMENTAL BIOLOGY, 1982, 89 (02) :299-308