Journal ArticleDOI
Altered Proteasomal Function in Sporadic Parkinson's Disease
Reads0
Chats0
TLDR
It is suggested that failure of the ubiquitin-proteasome system to adequately clear unwanted proteins may underlie vulnerability and degeneration of the SNc in both sporadic and familial PD.About:
This article is published in Experimental Neurology.The article was published on 2003-01-01. It has received 586 citations till now. The article focuses on the topics: Substantia nigra & Pars compacta.read more
Citations
More filters
Journal ArticleDOI
The roles of intracellular protein-degradation pathways in neurodegeneration
TL;DR: Improving macroautophagy with drugs such as rapamycin could offer a tractable therapeutic strategy for a number of late-onset neurodegenerative diseases.
Journal ArticleDOI
Molecular pathophysiology of parkinson's disease
TL;DR: Increasing evidence indicates that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system dysfunction may represent the principal molecular pathways or events that commonly underlie the pathogenesis of sporadic and familial forms of PD.
Journal ArticleDOI
The Role of Oxidative Stress in Parkinson’s Disease
TL;DR: Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD, but therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression.
Journal ArticleDOI
Aggregated α-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease
Wei Zhang,Tongguang Wang,Zhong Pei,David S. Miller,Xuefei Wu,Michelle L. Block,Belinda Wilson,Wanqin Zhang,Yong Zhou,Jau-Shyong Hong,Jing Zhang +10 more
TL;DR: The results suggest that nigral neuronal damage, regardless of etiology, may release aggregated α‐synuclein into substantia nigra, which activates microglia with production of proinflammatory mediators, thereby leading to persistent and progressive nigral neurodegeneration in PD.
Journal ArticleDOI
The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg.
Aaron Ciechanover,Patrik Brundin +1 more
TL;DR: Recent findings indicate that the ubiquitin-proteasome system is involved in the pathogenesis of Parkinson's, Alzheimer's, Huntington's, and Prion diseases as well as amyotrophic lateral sclerosis, which raises hopes for a better understanding of the pathogenetic mechanisms involved in these diseases and for the development of novel, mechanism-based therapeutic modalities.
References
More filters
Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
Rejko Krüger,Wilfried Kuhn,Thomas Müller,Dirk Woitalla,Manuel B. Graeber,Sigfried Kösel,Horst Przuntek,Jörg T. Epplen,Ludger Schöls,Olaf Riess +9 more
Journal ArticleDOI
The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.
W R Gibb,Andrew J. Lees +1 more
TL;DR: Associated pathological findings suggest that cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease.
Journal ArticleDOI
α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies
TL;DR: It is shown thatLewy bodies and Lewy neurites from Parkinson’s disease and dementia with Lewy bodies are stained strongly by antibodies directed against amino- terminal and carboxyl-terminal sequences of α-synuclein, showing the presence of full- length or close to full-length α- synuclein.
Journal ArticleDOI
The 26S Proteasome: A Molecular Machine Designed for Controlled Proteolysis
TL;DR: In eukaryotic cells, most proteins in the cytosol and nucleus are degraded via the ubiquitin-proteasome pathway, and the 26S proteasome is a 2-MDa molecular machine built from approximately 31 different subunits, which catalyzes protein degradation.
Related Papers (5)
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
α-Synuclein Locus Triplication Causes Parkinson's Disease
Andrew B. Singleton,Matthew J. Farrer,Joshua C. Johnson,Amanda Singleton,Stephen Hague,Jennifer M. Kachergus,Mary M. Hulihan,Terhi Peuralinna,Amalia Dutra,Robert L. Nussbaum,Sarah Lincoln,Anthony Crawley,Melissa Hanson,Demetrius M. Maraganore,Charles H. Adler,Mark R. Cookson,Manfred D. Muenter,Melisa J. Baptista,David Miller,J. Blancato,John Hardy,Katrina Gwinn-Hardy +21 more