TRPM7 and TRPM2-Candidate susceptibility genes for Western Pacific ALS and PD?
Meredith C Hermosura1, Ralph M Garruto
1Bekesy Laboratory of Neurobiology, Pacific Biosciences Research Center, University of Hawaii at Manoa, 1993 East-West Road, Honolulu, HI 96822, USA. meredith@pbrc.hawaii.edu
Abstract:
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.
Insights
TRPM7 and TRPM2 channels are implicated in neuronal death from oxidative stress, suggesting they are therapeutic targets for neurodegenerative diseases like ALS and PD. Their function is linked to mineral imbalances found in specific environments.
Area of Science:
- Neuroscience
- Ion Channel Biology
- Environmental Health
Background:
- TRPM7 and TRPM2 channels play roles in oxidative stress and neuronal death.
- These channels are linked to calcium (Ca2+) and magnesium (Mg2+) homeostasis, mitochondrial dysfunction, and immune responses.
- Neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) and Parkinsonism Dementia (PD) share these pathological mechanisms.
Purpose of the Study:
- To review the interconnected roles of TRPM7 and TRPM2 channels in neurodegeneration.
- To explore the gene-environment etiology of Western Pacific ALS and PD.
- To highlight the potential of TRPM7 and TRPM2 as therapeutic targets.
Main Methods:
- Literature review focusing on TRPM7 and TRPM2 channel function.
- Analysis of studies on oxidative stress, ion homeostasis, and neurodegeneration.
- Examination of environmental factors in Western Pacific ALS and PD.
Main Results:
- TRPM7 and TRPM2 are critical in processes underlying neurodegeneration.
- These channels are sensitive to disruptions in Ca2+ and Mg2+ homeostasis.
- Environmental factors, such as low Mg2+/Ca2+ and high transition metals, may impact TRPM7/TRPM2 function.
Conclusions:
- TRPM7 and TRPM2 channels are key players in neurodegenerative processes.
- Environmental mineral imbalances may contribute to neurodegeneration via TRPM7/TRPM2 dysfunction.
- Targeting TRPM7 and TRPM2 offers a potential therapeutic strategy for neurodegenerative diseases.
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