TY  - JOUR
AU  - Jucker, Mathias
AU  - Walker, Lary C
TI  - Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases.
JO  - Nature reviews / Neuroscience
VL  - 21
IS  - 10
SN  - 1097-6256
CY  - London
PB  - Nature Publ. Group58142
M1  - DZNE-2020-06553
SP  - 1341-1349
PY  - 2018
AB  - Many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by the progressive appearance of abnormal proteinaceous assemblies in the nervous system. Studies in experimental systems indicate that the assemblies originate from the prion-like seeded aggregation of specific misfolded proteins that proliferate and amass to form the intracellular and/or extracellular lesions typical of each disorder. The host in which the proteopathic seeds arise provides the biochemical and physiological environment that either supports or restricts their emergence, proliferation, self-assembly, and spread. Multiple mechanisms influence the spatiotemporal spread of seeds and the nature of the resulting lesions, one of which is the cellular uptake, release, and transport of seeds along neural pathways and networks. The characteristics of cells and regions in the affected network govern their vulnerability and thereby influence the neuropathological and clinical attributes of the disease. The propagation of pathogenic protein assemblies within the nervous system is thus determined by the interaction of the proteopathic agent and the host milieu.
KW  - Animals
KW  - Cell Communication
KW  - Humans
KW  - Neurodegenerative Diseases: metabolism
KW  - Neurodegenerative Diseases: pathology
KW  - Prions: metabolism
KW  - Prions: pathogenicity
KW  - Prions (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30258241
C2  - pmc:PMC6375686
DO  - DOI:10.1038/s41593-018-0238-6
UR  - https://pub.dzne.de/record/140231
ER  -