More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases.
Intracytoplasmic filamentous aggregates, such as neurofibrillary tangles in Alzheimer's disease and Lewy bodies in Parkinson's disease, are composed of the proteins tau and alpha-synuclein, respectively. These pathological inclusions are linked directly to the etiology and mechanisms of disease in a wide spectrum of neurodegenerative disorders, termed 'tauopathies' and 'synucleinopathies'. Emerging evidence indicates that there is frequent overlap of the pathological and clinical features of patients with tauopathies and synucleinopathies, thereby re-enforcing the notion that these disorders might be linked mechanistically. Indeed, several lines of investigation suggest that tau and alpha-synuclein might constitute a unique class of unstructured proteins that assemble predominantly into homopolymeric (rather than heteropolymeric) fibrils, which deposit mainly in separate amyloid inclusions, but occasionally deposit together. Thus, the ability of tau and alpha-synuclein to affect each other directly or indirectly might contribute to the overlap in the clinical and pathological features of tauopathies and synucleinopathies.
Lee
Virginia M-Y
VM
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, the University of Pennsylvania, Philadelphia, PA 19104-4283, USA. vmylee@mail.med.upenn.edu
Giasson
Benoit I
BI
Trojanowski
John Q
JQ
D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism*
D000682:Amyloid; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins