Parkinson's disease: Current and future challenges

被引:81
作者
Langston, JW [1 ]
机构
[1] Parkinsons Inst, Sunnyvale, CA 94089 USA
关键词
Parkinson's disease; genetic parkinsonism; alpha-synuclein; parkin; etiology; twins study; environment; epidemiology;
D O I
10.1016/S0161-813X(02)00098-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In 15 years, we will mark the 200th anniversary of the James Parkinson's original description of the disease that now bears his name (An Essay on the Shaking Palsy, Sherwood, Neely and Jones London, 1817). Perhaps, one of the most exciting but daunting questions we face at this moment is whether or not we can unravel the etiology of the disease by that time. If we are to accomplish such an ambitious goal, we must determine the resources that will be required to make it happen, and identify the areas of scientific focus that should receive the greatest attention. One issue that will have great bearing on the allocation of research resources relates to the relative roles of genes versus environment in disease causation. For reasons that will become clear in this article, this has a remained surprisingly controversial area. Ironically, this controversy has even spilled over to the very definition of Parkinson's disease, and even whether or not it should be considered a disease entity. In this article, the enduring "genes versus environment" debate is reviewed, with a goal of putting it into a broader perspective. Issues surrounding disease definition and terminology are also addressed in detail, because of the need to have clarity of thought and vision if research on the cause is to proceed in an orderly (and hopefully expeditious) manner Finally, issues relating future research directions are summarized, with the goal of identifying the pieces of the Parkinson's puzzle that are going to have to be put together if we are to solve this mysterious disease. (C) 2002 Published by Elsevier Science Inc.
引用
收藏
页码:443 / 450
页数:8
相关论文
共 45 条
[1]   A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe [J].
Abbas, N ;
Lücking, CB ;
Ricard, S ;
Dürr, A ;
Bonifati, V ;
De Michele, G ;
Bouley, S ;
Vaughan, JR ;
Gasser, T ;
Marconi, R ;
Broussolle, E ;
Brefel-Courbon, C ;
Harhangi, BS ;
Oostra, AB ;
Fabrizio, E ;
Böhme, GA ;
Pradier, L ;
Wood, NW ;
Filla, A ;
Meco, G ;
Denefle, P ;
Agid, Y ;
Brice, A .
HUMAN MOLECULAR GENETICS, 1999, 8 (04) :567-574
[2]  
BURCH PRJ, 1981, NEUROLOGY, V31, P500
[3]   Absence of mutations in the coding region of the α-synuclein gene in pathologically proven Parkinson's disease [J].
Chan, P ;
Jiang, X ;
Forno, LS ;
Di Monte, DA ;
Tanner, CM ;
Langston, JW .
NEUROLOGY, 1998, 50 (04) :1136-1137
[4]   Failure to find the α-synuclein gene missense mutation (G209A) in 100 patients with younger onset Parkinson's disease [J].
Chan, P ;
Tanner, CM ;
Jiang, X ;
Langston, JW .
NEUROLOGY, 1998, 50 (02) :513-514
[5]  
CHARCOT JM, 1878, LECT DIS NERVOUS SYS, V1
[6]   Concurrence of α-synuclein and tau brain pathology in the Contursi kindred [J].
Duda, JE ;
Giasson, BI ;
Mahon, ME ;
Miller, DC ;
Golbe, LI ;
Lee, VMY ;
Trojanowski, JQ .
ACTA NEUROPATHOLOGICA, 2002, 104 (01) :7-11
[7]   KINDREDS OF DOMINANTLY INHERITED PARKINSONS-DISEASE - KEYS TO THE RIDDLE [J].
DUVOISIN, RC ;
GOLBE, LI .
ANNALS OF NEUROLOGY, 1995, 38 (03) :355-356
[8]   Low frequency of α-synuclein mutations in familial Parkinson's disease [J].
Farrer, M ;
Wavrant-De Vrieze, F ;
Crook, R ;
Boles, L ;
Perez-Tur, J ;
Hardy, J ;
Johnson, WG ;
Steele, J ;
Maraganore, D ;
Gwinn, K ;
Lynch, T .
ANNALS OF NEUROLOGY, 1998, 43 (03) :394-397
[9]   Lewy bodies and parkinsonism in families with parkin mutations [J].
Farrer, M ;
Chan, P ;
Chen, R ;
Tan, L ;
Lincoln, S ;
Hernandez, D ;
Forno, L ;
Gwinn-Hardy, K ;
Petrucelli, L ;
Hussey, J ;
Singleton, A ;
Tanner, C ;
Hardy, J ;
Langston, JW .
ANNALS OF NEUROLOGY, 2001, 50 (03) :293-300
[10]   Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions [J].
Gilman, S ;
Sima, AAF ;
Junck, L ;
Kluin, KJ ;
Koeppe, RA ;
Lohman, ME ;
Little, R .
ANNALS OF NEUROLOGY, 1996, 39 (02) :241-255