Emerging pathways in genetic Parkinson's disease: tangles, Lewy bodies and LRRK2.
The last decade has seen clear links emerge between the genetic determinants and neuropathological hallmarks of parkinsonism and dementia, notably with the discovery of mutations in alpha-synuclein and tau. Following the description of mutations in LRRK2 linked to Parkinson's disease, characterized by variable pathology including either alpha-synuclein or tau deposition, it has been suggested that LRRK2 functions as an upstream regulator of Parkinson's disease pathogenesis. This minireview explores this model, in the context of our current understanding of the biochemistry of LRRK2, alpha-synuclein and tau.
Devine
Michael J
MJ
Department of Clinical Neuroscience, Imperial College London, UK.
Lewis
Patrick A
PA
D003704:Dementia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D016631:Lewy Bodies / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000502:physiology
C054369:MAPT protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases