The Ubiquitin Proteasome System as a Potential Target for the Treatment of Neurodegenerative Diseases

被引:25
作者
Ying, Zheng [1 ]
Wang, Hongfeng [1 ]
Wang, Guanghui [1 ]
机构
[1] Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Lab Mol Neuropathol, Suzhou 215123, Jiangsu, Peoples R China
关键词
Ubiquitin-proteasome system; deubiquitination; Alzheimer's disease; Parkinson's disease; amyotrophic lateral sclerosis; HELICAL-FILAMENT-TAU; AMYOTROPHIC-LATERAL-SCLEROSIS; SPORADIC PARKINSONS-DISEASE; AMYLOID BETA-PROTEIN; LINKED MUTANT SOD1; MOTOR-NEURON DEATH; ALPHA-SYNUCLEIN; ALZHEIMER-DISEASE; CU; ZN-SUPEROXIDE DISMUTASE; UBIQUITYLATED INCLUSIONS;
D O I
10.2174/1381612811319180013
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Neurodegenerative diseases are severe disorders characterized by progressive neurodegeneration in specific brain regions. The ubiquitin-proteasome system (UPS) is closely linked to neurodegenerative disease. In most cases, UPS impairment and dysregulation of the UPS components are frequently observed. Moreover, toxin-induced neurodegeneration produces neuronal cell death accompanied by decreased UPS function. These studies suggest an involvement of the UPS in these diseases. In this review, we summarize the changes to UPS components in neurodegenerative diseases and the association between the UPS and disease pathology. Dysfunction of the UPS results in the abnormal accumulation of proteins; thus, the UPS plays a critical role in disease pathogenesis. Drugs targeting specific components of the UPS may provide promising strategies for disease treatment.
引用
收藏
页码:3305 / 3314
页数:10
相关论文
共 139 条
  • [1] Diversity of Polyubiquitin Chains
    Adhikari, Anirban
    Chen, Zhijian J.
    [J]. DEVELOPMENTAL CELL, 2009, 16 (04) : 485 - 486
  • [2] Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice
    Anderson, C
    Crimmins, S
    Wilson, JA
    Korbel, GA
    Ploegh, HL
    Wilson, SM
    [J]. JOURNAL OF NEUROCHEMISTRY, 2005, 95 (03) : 724 - 731
  • [3] Phosphorylation of Ser-129 is the dominant pathological modification of α-synuclein in familial and sporadic Lewy body disease
    Anderson, John P.
    Walker, Donald E.
    Goldstein, Jason M.
    de laat, Rian
    Banducci, Kelly
    Caccavello, Russell J.
    Barbour, Robin
    Huang, Jiping
    Kling, Kristin
    Lee, Michael
    Diep, Linnea
    Keim, Pamela S.
    Shen, Xiaofeng
    Chataway, Tim
    Schlossmacher, Michael G.
    Seubert, Peter
    Schenk, Dale
    Sinha, Sukanto
    Gai, Wei Ping
    Chilcote, Tamie J.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (40) : 29739 - 29752
  • [4] Immune and non-immune functions of the immunoproteasome
    Angeles, Arkhjamil
    Fung, Gabriel
    Luo, Honglin
    [J]. FRONTIERS IN BIOSCIENCE-LANDMARK, 2012, 17 : 1904 - 1916
  • [5] UCH-L1 aggresome formation in response to proteasome impairment indicates a role in inclusion formation in Parkinson's disease
    Ardley, HC
    Scott, GB
    Rose, SA
    Tan, NGS
    Robinson, PA
    [J]. JOURNAL OF NEUROCHEMISTRY, 2004, 90 (02) : 379 - 391
  • [6] AUER IA, 1995, ACTA NEUROPATHOL, V90, P547
  • [7] Role of ubiquitylation and USP8-dependent deubiquitylation in the endocytosis and lysosomal targeting of plasma membrane KCa3.1
    Balut, Corina M.
    Loch, Christian M.
    Devor, Daniel C.
    [J]. FASEB JOURNAL, 2011, 25 (11) : 3938 - 3948
  • [8] Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies
    Barrachina, M
    Castaño, E
    Dalfó, E
    Maes, T
    Buesa, C
    Ferrer, I
    [J]. NEUROBIOLOGY OF DISEASE, 2006, 22 (02) : 265 - 273
  • [9] Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies
    Bedford, Lynn
    Hay, David
    Devoy, Anny
    Paine, Simon
    Powe, Des G.
    Seth, Rashmi
    Gray, Trevor
    Topham, Ian
    Fone, Kevin
    Rezvani, Nooshin
    Mee, Maureen
    Soane, Tim
    Layfield, Robert
    Sheppard, Paul W.
    Ebendal, Ted
    Usoskin, Dmitry
    Lowe, James
    Mayer, R. John
    [J]. JOURNAL OF NEUROSCIENCE, 2008, 28 (33) : 8189 - 8198
  • [10] Pen-2 is sequestered in the endoplasmic reticulum and subjected to ubiquitylation and proteasome-mediated degradation in the absence of presenilin
    Bergman, A
    Hansson, EM
    Pursglove, SE
    Farmery, MR
    Lannfelt, L
    Lendahl, U
    Lundkvist, J
    Näslund, J
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (16) : 16744 - 16753