Publication Date:
2012-11-20
Description:
Parkinson's disease is characterized by abundant alpha-synuclein (alpha-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss of midbrain dopamine neurons. However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear. Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic alpha-Syn fibrils led to the cell-to-cell transmission of pathologic alpha-Syn and Parkinson's-like Lewy pathology in anatomically interconnected regions. Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta, but not in the adjacent ventral tegmental area, and was accompanied by reduced dopamine levels culminating in motor deficits. This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic alpha-Syn and the cardinal features of Parkinson's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552321/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552321/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luk, Kelvin C -- Kehm, Victoria -- Carroll, Jenna -- Zhang, Bin -- O'Brien, Patrick -- Trojanowski, John Q -- Lee, Virginia M-Y -- NS053488/NS/NINDS NIH HHS/ -- P50 NS053488/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 16;338(6109):949-53. doi: 10.1126/science.1227157.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-4283, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23161999" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cells, Cultured
;
Corpus Striatum/drug effects/*metabolism/pathology
;
Dopamine
;
Dopaminergic Neurons/drug effects/metabolism/pathology
;
Injections
;
Lewy Bodies/drug effects/*metabolism/pathology
;
Mice
;
Parkinsonian Disorders/*metabolism/pathology
;
Protein Folding
;
Protein Transport
;
Recombinant Proteins/administration & dosage/chemistry/metabolism
;
Substantia Nigra/drug effects/metabolism/pathology
;
alpha-Synuclein/administration & dosage/chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
