Journal ArticleDOI
Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation.
Jia-Yi Li,Elisabet Englund,Janice L. Holton,Denis Soulet,Peter Hagell,Andrew J. Lees,Tammaryn Lashley,Niall Quinn,Stig Rehncrona,Anders Björklund,Håkan Widner,Tamas Revesz,Olle Lindvall,Patrik Brundin +13 more
TLDR
Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11–16 years) developed α-synuclein–positive Lewy bodies in grafted neurons, providing the first evidence, to the authors' knowledge, that the disease can propagate from host to graft cells.Abstract:
Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.read more
Citations
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Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein.
Paula Desplats,He Jin Lee,Eun Jin Bae,Christina Patrick,Edward Rockenstein,Leslie Crews,Brian Spencer,Eliezer Masliah,Seung-Jae Lee +8 more
TL;DR: It is shown that α-synuclein is transmitted via endocytosis to neighboring neurons and neuronal precursor cells, forming Lewy-like inclusions, which provide critical insights into the mechanism of pathological progression in PD and other proteinopathies.
Journal ArticleDOI
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
TL;DR: As a unifying pathogenic principle, the prion paradigm suggests broadly relevant therapeutic directions for a large class of currently intractable diseases.
Journal ArticleDOI
Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death.
Laura A. Volpicelli-Daley,Kelvin C. Luk,Tapan P. Patel,Selcuk A. Tanik,Dawn M. Riddle,Anna Stieber,David F. Meaney,John Q. Trojanowski,Virginia M.-Y. Lee +8 more
TL;DR: It is demonstrated that preformed fibrils generated from full-length and truncated recombinant α-syn enter primary neurons, probably by adsorptive-mediated endocytosis, and promote recruitment of soluble endogenousα-syn into insoluble PD-like LBs and LNs.
Journal ArticleDOI
The Glymphatic System: A Beginner’s Guide
TL;DR: The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system.
Journal ArticleDOI
The Biology of Proteostasis in Aging and Disease
TL;DR: The composition, function, and organizational properties of the PN are reviewed in the context of individual cells and entire organisms and the mechanisms by which disruption of thePN, and related stress response pathways, contributes to the initiation and progression of disease are discussed.
References
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Journal ArticleDOI
Staging of brain pathology related to sporadic Parkinson’s disease
TL;DR: This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
Journal ArticleDOI
Transplantation of embryonic dopamine neurons for severe Parkinson's disease.
Curt R. Freed,Paul Greene,Robert E. Breeze,Wei-Yann Tsai,William DuMouchel,Richard Kao,Sandra Dillon,Howard Winfield,Sharon Culver,John Q. Trojanowski,David Eidelberg,Stanley Fahn +11 more
TL;DR: After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa.
Journal ArticleDOI
A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease†
C. Warren Olanow,Christopher G. Goetz,Jeffrey H. Kordower,A. Jon Stoessl,Vesna Sossi,Mitchell F. Brin,Kathleen M. Shannon,G. Michael Nauert,Daniel P. Perl,James Godbold,Thomas B. Freeman +10 more
TL;DR: Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on results, and Stratification based on disease severity showed a treatment effect in milder patients.
Journal ArticleDOI
Phosphorylation of Ser-129 Is the Dominant Pathological Modification of α-Synuclein in Familial and Sporadic Lewy Body Disease
John P. Anderson,Donald Walker,Jason Goldstein,Rian de Laat,Kelly Banducci,Russell J. Caccavello,Robin Barbour,Jiping Huang,Kristin Kling,Michael K. Lee,Linnea Diep,Pamela S. Keim,Xiaofeng Shen,Tim Chataway,Michael G. Schlossmacher,Peter A. Seubert,Dale B. Schenk,Sukanto Sinha,Wei Ping Gai,Tamie J. Chilcote +19 more
TL;DR: A comprehensive, unbiased inventory of synuclein forms present in Lewy bodies from patients with dementia with Lewy body was carried out using two-dimensional immunoblot analysis, novel enzyme-linked immunosorbent assays with modification-specific Synuclein antibodies, and mass spectroscopy as mentioned in this paper.
Transplantation of embryonic dopamine neurons for severe parkinson's disease
R. F Reed,P Aul E. G Reene,R Obert E. B Reeze,W Ei,W Illiam D U M Ouchel,R Ichard K Ao,W Infield,S Haron C Ulver,J Ohn Q. T Rojanowski,D Avid E Idelberg,S Tanley F Ahn +10 more
TL;DR: For example, in this paper, the authors randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or undergo sham surgery; all were to be followed in a double-blind manner for one year.