Analysis of common molecular pathogenesis in Neuroacanthocytosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07606
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kagoshima University
• Principal Investigator: NAKAMURA Masayuki 鹿児島大学, 医歯学域医学系, 教授 (90332832)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 神経有棘赤血球症 / 有棘赤血球舞踏病 / McLeod症候群 / chorein / VPS13A / XK / XK蛋白質

Outline of Final Research Achievements

Neuroacanthocytosis (NA) is used to describe a condition that combines neurological symptoms and acanthocytosis. The core group of NA is represented by chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). ChAc is caused by a loss-of-function mutation in the VPS13A gene, resulting in loss of the gene product chorein, and MLS is caused by a loss-of-function mutation in the XK gene on the X chromosome, resulting in loss of the XK protein. In all six MLS cases, chorein expression was decreased in the erythrocyte membrane fraction, and the interaction between XK protein and chorein was indicated in cultured cells, suggesting that disruption of the cytoskeletal interaction and the mitochondrial quality maintenance mechanism of chorein are common molecular pathogenesis of NA.

Free Research Field

精神神経科学

Academic Significance and Societal Importance of the Research Achievements

神経有棘赤血球症の代表疾患である有棘赤血球舞踏病とMcLeod症候群は臨床症状が酷似しており、両疾患ともにハンチントン病類似の精神神経症状と末梢血赤血球に有棘赤血球症を呈し、共通する分子病態の存在が示唆される。これら疾患の共通分子病態を明らかにすることによって、両疾患に共通する治療法の開発の足掛かりとなり、両疾患は高率に精神症状を来すことから、精神疾患の病態解明や治療法開発の一助にもなる。