Open AccessDifferent α-synuclein prion strains cause dementia with Lewy bodies and multiple system atrophy
Author(s) -
Jacob I. Ayers,
Joanne Lee,
Octovia Monteiro,
Amanda L. Woerman,
Ann Lazar,
Carlo Condello,
Nick A. Paras,
Stanley B. Prusiner
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2113489119
Subject(s) - dementia with lewy bodies , synucleinopathies , hek 293 cells , mutant , neurodegeneration , biology , amyloid (mycology) , mutation , alpha synuclein , virology , transgene , atrophy , genetically modified mouse , microbiology and biotechnology , parkinson's disease , genetics , disease , cell culture , dementia , gene , medicine , pathology , botany
Significance Dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are caused by α-synuclein prions that differ from each other and from those causing Parkinson’s disease (PD). DLB prions differ in their infectivity from those causing MSA or PD. The wild-type, normal version of the α-synuclein protein has the acidic amino acid glutamate (E) at residue 46, while in cases of inherited PD, it is mutated to the basic amino acid lysine (K). Using genetically engineered α-synuclein, we identified unique conditions for propagating MSA and DLB prions. Being able to distinguish among strains of naturally occurring α-synuclein prions may make it possible to develop strain-specific therapeutics for MSA, DLB, and PD.