TRPM7 and TRPM2-Candidate susceptibility genes for Western Pacific ALS and PD?
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 (Ca(2+)) and magnesium (Mg(2+)) 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 Mg(2+) and Ca(2+), yet high in transition metals, creates a condition that could affect the proper function of these two channels.
Hermosura
Meredith C
MC
Bekesy Laboratory of Neurobiology, Pacific Biosciences Research Center, University of Hawaii at Manoa, 1993 East-West Road, Honolulu, HI 96822, USA. meredith@pbrc.hawaii.edu
Garruto
Ralph M
RM
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D016923:Cell Death; D003704:Dementia / Q000235:genetics*; D004777:Environment; D020022:Genetic Predisposition to Disease; D006801:Humans; D017628:Microglia / Q000378:metabolism; D008928:Mitochondria / Q000473:pathology; D009474:Neurons / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D020734:Parkinsonian Disorders / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D026361:Reactive Nitrogen Species / Q000494:pharmacology; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D026361:Reactive Nitrogen Species; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human