Tubulin seeds alpha-synuclein fibril formation.
Increasing evidence suggests that alpha-synuclein is a common pathogenic molecule in several neurodegenerative diseases, particularly in Parkinson's disease. To understand alpha-synuclein pathology, we investigated molecules that interact with alpha-synuclein in human and rat brains and identified tubulin as an alpha-synuclein binding/associated protein. Tubulin co-localized with alpha-synuclein in Lewy bodies and other alpha-synuclein-positive pathological structures. Tubulin initiated and promoted alpha-synuclein fibril formation under physiological conditions in vitro. These findings suggest that an interaction between tubulin and alpha-synuclein might accelerate alpha-synuclein aggregation in diseased brains, leading to the formation of Lewy bodies.
Alim
Muhammad Abdul
MA
Department of Neural Plasticity, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo 156-8585, Japan.
Hossain
Mosammat Shahanara
MS
Arima
Kunimasa
K
Takeda
Kazuya
K
Izumiyama
Yoko
Y
Nakamura
Minako
M
Kaji
Hiroyuki
H
Shinoda
Tomotaka
T
Hisanaga
Shinichi
S
Ueda
Kenji
K
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D051381:Rats; D051843:Synucleins; D014404:Tubulin / Q000378:metabolism*; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497606:Snca protein, rat; D051843:Synucleins; D014404:Tubulin; D051844:alpha-Synuclein