Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity.

Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity. Research Abstract Details 

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Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity. Abstract Text:

Masafumi Ihara,Nobuyuki Yamasaki,Akari Hagiwara,Ai Tanigaki,Ayumi Kitano,Rie Hikawa,Hidekazu Tomimoto,Makoto Noda,Masashi Takanashi,Hideo Mori,Nobutaka Hattori,Tsuyoshi Miyakawa,Makoto Kinoshita,

In Parkinson disease (PD), alpha-synuclein aggregates called Lewy bodies often involve and sequester Septin4 (Sept4), a polymerizing scaffold protein. However, the pathophysiological significance of this phenomenon is unclear. Here, we show the physiological association of Sept4 with alpha-synuclein, the dopamine transporter, and other presynaptic proteins in dopaminergic neurons; mice lacking Sept4 exhibit diminished dopaminergic neurotransmission due to scarcity of these presynaptic proteins. These data demonstrate an important role for septin scaffolds in the brain. In transgenic mice that express human alpha-synuclein(A53T) (a mutant protein responsible for familial PD), loss of Sept4 significantly enhances neuropathology and locomotor deterioration. In this PD model, insoluble deposits of Ser(129)-phosphorylated alpha-synuclein(A53T) are negatively correlated with the dosage of Sept4. In vitro, direct association with Sept4 protects alpha-synuclein against self-aggregation and Ser(129) phosphorylation. Taken together, these data show that Sept4 may be involved in PD as a dual susceptibility factor, as its insufficiency can diminish dopaminergic neurotransmission and enhance alpha-synuclein neurotoxicity.

Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity. Publishing Authors By Initials

M Ihara,N Yamasaki,A Hagiwara,A Tanigaki,A Kitano,R Hikawa,H Tomimoto,M Noda,M Takanashi,H Mori,N Hattori,T Miyakawa,M Kinoshita,

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Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Neuron

VOLUME: 53

Page Numbers: 519-33

Journal Abbreviation: Neuron

ISSN: 0896-6273

DAY: 15

MONTH: Feb

YEAR: 2007

Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity. Information

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LANGUAGE: eng

NlmUniqueID: 8809320

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Grant and Affiliation Information for Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity.

AFFILIATION: Biochemistry and Cell Biology Unit, HMRO, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo, Kyoto 606-8501, Japan.

Country: United States

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MEDLINETA: Neuron

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