TRPM7 and TRPM2—Candidate susceptibility genes for Western Pacific ALS and PD?

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• 作者：Meredith C. Hermosura ; Ralph M. Garruto
• 关键词：TRPM7 ; TRPM2 ; Western Pacific ALS ; Parkinsonism Dementia ; Oxidative stress ; Neurodegeneration ; Ca²⁺ and Mg²⁺ homeostasis ; Mitochondrial dysfunction ; Microglial activation
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2007
• 期刊代码：19_09254439
• 类别：bio
• 出版时间：August 2007
• 卷：1772
• 期：8
• 页码：822-835
• 文件大小：262 K

摘要

Recent findings implicating TRPM7 and TRPM2 in oxidative stress-induced neuronal death thrust these channels into the spotlight as possible therapeutic targets for neurodegenerative diseases. In this review, we describe how the functional properties of TRPM7 and TRPM2 are interconnected with calcium (Ca²⁺) and magnesium (Mg²⁺) homeostasis, oxidative stress, mitochondrial dysfunction, and immune mechanisms, all principal suspects in neurodegeneration. We focus our discussion on Western Pacific Amyotrophic Lateral Sclerosis (ALS) and Parkinsonism Dementia (PD) because extensive studies conducted over the years strongly suggest that these diseases are ideal candidates for a gene-environment model of etiology. The unique mineral environment identified in connection with Western Pacific ALS and PD, low Mg²⁺ and Ca²⁺, yet high in transition metals, creates a condition that could affect the proper function of these two channels.