Tokyo Metropolitan Institute of Medical Science

Makiko Yamashita

Masato Hasegawa

Takashi Nonaka

Haruhiko Akiyama

Tetsuaki Arai

Masami Masuda

The purpose of the present invention is to develop a method for amplifying in vitro to a large amount of a homogenous insoluble aggregate that is equivalent to an insoluble aggregate formed in the brain of a patient. A method of producing an insoluble aggregate including TDP-43 protein and fragments thereof according to the present invention includes the steps of: (1) introducing an insoluble fraction originated from the brain of a neurodegenerative disease patient into a cell culture in which the intact TDP-43 protein can be expressed in a constitutive manner; (2) culturing the cultured cell into which the insoluble fraction has been introduced; and (3) separating an insoluble fraction from the cultured cell. Optionally, the method may additionally include a step of amplifying the insoluble aggregate of the neurodegenerative-disease-related protein in the cultured cell.

Method for producing insoluble aggregate of neurodegenerative-disease-related protein

Disclosed is a transformed cell (a cell model) which can form a cytoplasmic inclusion body derived from TAR DNA-binding protein of 43 kDa (TDP-43) that is found in the brain of a patient suffering from a neurodegenerative disease such as FTLD and ALS. The transformed cell is characterized by having, introduced therein, a promoter capable of functioning in a host cell and a mutant TDP-43 gene.

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Tokyo, Japan

Makiko Yamashita