The Role of alpha-synuclein assembly and metabolism in the pathogenesis of Lewy body disease.
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are members of a family of disorders characterized by the presence of inclusion bodies, or Lewy bodies (LBs), filled with aggregates of alpha-synuclein. These diseases are a leading cause of movement disorders and dementia in the aging population, and it is crucial to understand the factors leading to the accumulation and assembly of these alpha-synuclein aggregates. Previous studies have uncovered much about the factors leading to aggregation and the mechanisms causing neurotoxicity of these inclusion bodies; however, little is known about factors that promote the degradation and prevent the aggregation of alpha-synuclein. The present article provides a review of recent efforts in the investigation of factors involved in alpha-synuclein metabolism and the mechanisms involved in preventing accumulation of alpha-synuclein and degrading this molecule. Understanding these processes might provide targets for the development of novel therapies for disorders such as DLB and PD.
Hashimoto
Makoto
M
Department of Neurosciences, University of California San Diego, La Jolla, CA 92093-0624, USA.
Kawahara
Kohichi
K
Bar-On
Pazit
P
Rockenstein
Edward
E
Crews
Leslie
L
Masliah
Eliezer
E
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics / Q000378:metabolism; D020961:Lewy Body Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051843:Synucleins; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D025801:Ubiquitin; D051844:alpha-Synuclein; D046988:Proteasome Endopeptidase Complex