Neurodegenerative diseases: New concepts of pathogenesis and their therapeutic implications

被引:311
作者
Skovronsky, Daniel M. [1 ]
Lee, Virginia M. -Y.
Trojanowskiz, John Q.
机构
[1] Avid Radiopharmaceut Inc, Philadelphia, PA 19104 USA
[2] Univ Penn, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA
关键词
amyloid; Alzheimer's disease; Parkinson's disease; neurodegeneration misfolding;
D O I
10.1146/annurev.pathol.1.110304.100113
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Neurodegenerative diseases as diverse as Alzheimer's, Parkinson's, and Creutzfeldt-Jakob disease share a common pathogenetic mechanism involving aggregation and deposition of misfolded proteins, which leads to progressive central nervous system disease. Although the type of aggregated protein and the regional and cellular distribution of deposition vary from disease to disease, these disorders may all be linked by similar pathways of protein aggregation with fibril formation and amyloid deposition. This perspective on pathogenesis suggests that a wide variety of neurodegenerative diseases can be grouped mechanistically as brain amyloidoses, an outlook that yields novel insights into potential therapeutic approaches that may be applicable across the broad spectrum of neurodegenerative disease.
引用
收藏
页码:151 / 170
页数:20
相关论文
共 126 条
[1]   Mechanisms of suppression of α-synuclein neurotoxicity by geldanamycin in Drosophila [J].
Auluck, PK ;
Meulener, MC ;
Bonini, NM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (04) :2873-2878
[2]   Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease [J].
Auluck, PK ;
Chan, HYE ;
Trojanowski, JQ ;
Lee, VMY ;
Bonini, NM .
SCIENCE, 2002, 295 (5556) :865-868
[3]  
Baba M, 1998, AM J PATHOL, V152, P879
[4]   Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease [J].
Bard, F ;
Cannon, C ;
Barbour, R ;
Burke, RL ;
Games, D ;
Grajeda, H ;
Guido, T ;
Hu, K ;
Huang, JP ;
Johnson-Wood, K ;
Khan, K ;
Kholodenko, D ;
Lee, M ;
Lieberburg, I ;
Motter, R ;
Nguyen, M ;
Soriano, F ;
Vasquez, N ;
Weiss, K ;
Welch, B ;
Seubert, P ;
Schenk, D ;
Yednock, T .
NATURE MEDICINE, 2000, 6 (08) :916-919
[5]   HYDROGEN-PEROXIDE MEDIATES AMYLOID-BETA PROTEIN TOXICITY [J].
BEHL, C ;
DAVIS, JB ;
LESLEY, R ;
SCHUBERT, D .
CELL, 1994, 77 (06) :817-827
[6]   Chronic systemic pesticide exposure reproduces features of Parkinson's disease [J].
Betarbet, R ;
Sherer, TB ;
MacKenzie, G ;
Garcia-Osuna, M ;
Panov, AV ;
Greenamyre, JT .
NATURE NEUROSCIENCE, 2000, 3 (12) :1301-1306
[7]   Glycogen synthase kinase 3: a drug target for CNS therapies [J].
Bhat, RV ;
Haeberlein, SLB ;
Avila, J .
JOURNAL OF NEUROCHEMISTRY, 2004, 89 (06) :1313-1317
[8]   Inhibition of fibril formation and toxicity of a fragment of α-synuclein by an N-methylated peptide analogue [J].
Bodles, AM ;
El-Agnaf, OMA ;
Greer, B ;
Guthrie, DJS ;
Irvine, GB .
NEUROSCIENCE LETTERS, 2004, 359 (1-2) :89-93
[9]  
Braak H., 2002, J NEUROL S3, V249, pIII/1
[10]   Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset [J].
Brookmeyer, R ;
Gray, S ;
Kawas, C .
AMERICAN JOURNAL OF PUBLIC HEALTH, 1998, 88 (09) :1337-1342