Tags

Type your tag names separated by a space and hit enter

Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions.
Neurobiol Dis. 2009 Sep; 35(3):385-98.ND

Abstract

We explored the relationship between ubiquitin proteasome system (UPS) and lysosomal markers and the formation of alpha-synuclein (alpha-syn) inclusions in nigral neurons in Parkinson disease (PD). Lysosome Associated Membrane Protein 1(LAMP1), Cathepsin D (CatD), and Heat Shock Protein73 (HSP73) immunoreactivity were significantly decreased within PD nigral neurons when compared to age-matched controls. This decrease was significantly greater in nigral neurons that contained alpha-syn inclusions. Immunoreactivity for 20S proteasome was similarly reduced in PD nigral neurons, but only in cells that contained inclusions. In aged control brains, there is staining for alpha-syn protein, but it is non-aggregated and there is no difference in LAMP1, CatD, HSP73 or 20S proteasome immunoreactivity between alpha-syn positive or negative neuromelanin-laden nigral neurons. Targeting over-expression of mutant human alpha-syn in the rat substantia nigra using viral vectors revealed that lysosomal and proteasomal markers were significantly decreased in the neurons that displayed alpha-syn-ir inclusions. These findings suggest that alpha-syn aggregation is a key feature associated with decline of proteasome and lysosome and support the hypothesis that cell degeneration in PD involves proteosomal and lysosomal dysfunction, impaired protein clearance, and protein accumulation and aggregation leading to cell death.

Authors+Show Affiliations

Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19505575

Citation

Chu, Yaping, et al. "Alterations in Lysosomal and Proteasomal Markers in Parkinson's Disease: Relationship to Alpha-synuclein Inclusions." Neurobiology of Disease, vol. 35, no. 3, 2009, pp. 385-98.
Chu Y, Dodiya H, Aebischer P, et al. Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions. Neurobiol Dis. 2009;35(3):385-98.
Chu, Y., Dodiya, H., Aebischer, P., Olanow, C. W., & Kordower, J. H. (2009). Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions. Neurobiology of Disease, 35(3), 385-98. https://doi.org/10.1016/j.nbd.2009.05.023
Chu Y, et al. Alterations in Lysosomal and Proteasomal Markers in Parkinson's Disease: Relationship to Alpha-synuclein Inclusions. Neurobiol Dis. 2009;35(3):385-98. PubMed PMID: 19505575.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions. AU - Chu,Yaping, AU - Dodiya,Hemraj, AU - Aebischer,Patrick, AU - Olanow,C Warren, AU - Kordower,Jeffrey H, Y1 - 2009/06/06/ PY - 2009/04/27/received PY - 2009/05/28/revised PY - 2009/05/30/accepted PY - 2009/6/10/entrez PY - 2009/6/10/pubmed PY - 2009/12/16/medline SP - 385 EP - 98 JF - Neurobiology of disease JO - Neurobiol Dis VL - 35 IS - 3 N2 - We explored the relationship between ubiquitin proteasome system (UPS) and lysosomal markers and the formation of alpha-synuclein (alpha-syn) inclusions in nigral neurons in Parkinson disease (PD). Lysosome Associated Membrane Protein 1(LAMP1), Cathepsin D (CatD), and Heat Shock Protein73 (HSP73) immunoreactivity were significantly decreased within PD nigral neurons when compared to age-matched controls. This decrease was significantly greater in nigral neurons that contained alpha-syn inclusions. Immunoreactivity for 20S proteasome was similarly reduced in PD nigral neurons, but only in cells that contained inclusions. In aged control brains, there is staining for alpha-syn protein, but it is non-aggregated and there is no difference in LAMP1, CatD, HSP73 or 20S proteasome immunoreactivity between alpha-syn positive or negative neuromelanin-laden nigral neurons. Targeting over-expression of mutant human alpha-syn in the rat substantia nigra using viral vectors revealed that lysosomal and proteasomal markers were significantly decreased in the neurons that displayed alpha-syn-ir inclusions. These findings suggest that alpha-syn aggregation is a key feature associated with decline of proteasome and lysosome and support the hypothesis that cell degeneration in PD involves proteosomal and lysosomal dysfunction, impaired protein clearance, and protein accumulation and aggregation leading to cell death. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/19505575/Alterations_in_lysosomal_and_proteasomal_markers_in_Parkinson's_disease:_relationship_to_alpha_synuclein_inclusions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(09)00135-1 DB - PRIME DP - Unbound Medicine ER -