Defects in trafficking bridge Parkinson's disease pathology and genetics.
Parkinson's disease is a debilitating, age-associated movement disorder. A central aspect of the pathophysiology of Parkinson's disease is the progressive demise of midbrain dopamine neurons and their axonal projections, but the underlying causes of this loss are unclear. Advances in genetics and experimental model systems have illuminated an important role for defects in intracellular transport pathways to lysosomes. The accumulation of altered proteins and damaged mitochondria, particularly at axon terminals, ultimately might overwhelm the capacity of intracellular disposal mechanisms. Cell-extrinsic mechanisms, including inflammation and prion-like spreading, are proposed to have both protective and deleterious functions in Parkinson's disease.
Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.|Department of Neurology, Columbia University, New York, New York 10032, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York 10032, USA.
Asa
A
Abeliovich
Department of Genetics, Stanford University, Stanford, California 94305, USA.
Aaron D
AD
Gitler
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D004705:Endocytosis; D005962:Glucosylceramidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D011328:Prions / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D011328:Prions; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D005962:Glucosylceramidase