Familial Parkinson Mutant α-Synuclein Causes Dopamine Neuron Dysfunction in Transgenic Caenorhabditis elegans

• DOI: 10.1074/jbc.m504860200
• Publication Date: 2005-11-01T01:43:55Z
• Authors: Tomoki Kuwahara; Akihiko Koyama; Keiko Gengyo-Ando; Mayumi Masuda; Hisatomo Kowa; Makoto Tsunoda; Shohei Mitani; Takeshi Iwatsubo
• Keywords: Synuclein; Neurite

Mutations in alpha-synuclein gene cause familial form of Parkinson disease, and deposition wild-type as Lewy bodies occurs a hallmark lesion sporadic disease dementia with bodies, implicating the pathogenesis related neurodegenerative diseases. Dopamine neurons substantia nigra are major site neurodegeneration associated disease. Here we establish transgenic Caenorhabditis elegans (TG worms) that overexpresses or mutant human dopamine neurons. The TG worms exhibit accumulation cell neurites neurons, EGFP labeling dendrites is often diminished expressing disease-linked A30P A53T alpha-synuclein, without overt loss neuronal bodies. Notably, show failure modulation locomotory rate response to food, which has been attributed function This behavioral abnormality was accompanied by reduction content treatable administration dopamine. These phenotypes were not seen upon expression beta-synuclein. present neuron-specific dysfunction caused would be relevant genetic compound screenings aiming at elucidation pathological cascade therapeutic strategies for