LRRK2: a common pathway for parkinsonism, pathogenesis and prevention?
The presence of alpha-synuclein Lewy body pathology is used to distinguish Parkinson's disease from parkinsonism, for which a broader spectrum of neuropathologies, including tau-immunopositive neurofibrillary tangles and ubiquitin inclusions, might accompany nigral neuronal loss. These neuropathologies define the endpoint of many neurodegenerative disorders but might be symptomatic rather than causative. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) were recently discovered in late-onset parkinsonism, the phenotype of which can be clinically and pathologically indistinguishable from Parkinson's disease. However, in some kindreds with LRRK2- associated disease, pathologically distinct forms of parkinsonism, including nigral neuronal loss with Lewy body disease or tau-immunopositive neurofibrillary tangles, were discovered. Understanding the molecular function of the LRRK2 protein and its associated pathways might elucidate the switch between Lewy body pathology and neurofibrillary tangles, and holds promise for prospective therapeutics that might slow or halt progression of many forms of parkinsonism.
Taylor
Julie P
JP
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
Mata
Ignacio F
IF
Farrer
Matt J
MJ
D000818:Animals; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D016631:Lewy Bodies / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D016874:Neurofibrillary Tangles / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
D025801:Ubiquitin; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases