TRPM7 and its role in neurodegenerative diseases

Abstract

Calcium (Ca2+) and magnesium (Mg2+) ions have been shown to play an important role in regulating various neuronal functions. In the present review we focus on the emerging role of transient potential melastatin-7 (TRPM7) channel in not only regulating Ca2+ and Mg2+ homeostasis necessary for biological functions, but also how alterations in TRPM7 function/expression could induce neurodegeneration. Although eight TRPM channels have been identified, the channel properties, mode of activation, and physiological responses of various TRPM channels are quite distinct. Among the known 8 TRPM channels only TRPM6 and TRPM7 channels are highly permeable to both Ca2+ and Mg2+; however here we will only focus on TRPM7 as unlike TRPM6, TRPM7 channels are abundantly expressed in neuronal cells. Importantly, the discrepancy in TRPM7 channel function and expression leads to various neuronal diseases such as Alzheimer disease (AD) and Parkinson disease (PD). Further, it is emerging as a key factor in anoxic neuronal death and in other neurodegenerative disorders. Thus, by understanding the precise involvement of the TRPM7 channels in different neurodegenerative diseases and by understanding the factors that regulate TRPM7 channels, we could uncover new strategies in the future that could evolve as new drug therapeutic targets for effective treatment of these neurodegenerative diseases.

Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7‐mediated chondroitin sulfate proteoglycan production

“…Overactive neuronal TRPM7 leads to calcium-induced cytotoxicity during cerebral ischaemia (Aarts et al, 2003;Hermosura et al, 2005) and changes in the function of TRPM7 may either be caused by genetic alterations or changes in regulatory pathways of TRPM7 channel activity (Sun et al, 2015). Enhanced astrocytic TRPM7 protein expression may be the result of the inflammatory environment and the production of TGF-β1 by activated glia and infiltrated macrophages (Miljkovi c et al, 2011;van Horssen et al, 2006).…”

“…Within this class of ion channels, transient receptor potential (TRP) channels have been recognized to be involved in numerous pathological conditions, including neurological disorders (Jordt & Ehrlich, 2007). Interestingly, previous reports identified Transient Receptor Potential Melastatin 7 (TRPM7), a member of the TRP channel family with inherent kinase activity, to be involved Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis and stroke via both Ca 2+ and Mg 2+ dependent and independent mechanisms (Sun, Sukumaran, Schaar, & Singh, 2015). In addition, comparative gene expression analysis identified TRPM7 as one of the common upregulated genes in Alzheimer's disease and MS compared with healthy controls (Tseveleki et al, 2010).…”

Prostaglandin E2 increases migration and proliferation of human glioblastoma cells by activating transient receptor potential melastatin 7 channels

“…The transient receptor potential melastatin 7 (TRPM7) is a cation channel with a functional serine/threonine protein kinase domain in its C‐terminal . TRPM7 is ubiquitously expressed and plays important roles in various pathological and physiological processes, including Mg 2+ homeostasis, cell proliferation, embryonic development and differentiation, cancer, ischemic stroke, cardiovascular and neurodegenerative diseases (for review, see reference ). Inhibition of TRPM7 has been extensively studied.…”

“…------------------------------------------------------------------------------------- 13,14 TRPM7 is ubiquitously expressed and plays important roles in various pathological and physiological processes, including Mg 2+ homeostasis, cell proliferation, embryonic development and differentiation, cancer, ischemic stroke, cardiovascular and neurodegenerative diseases (for review, see reference 15,16).…”

TRPC Channels and Parkinson’s Disease

“…Calcium (Ca 2+ ) is an important element that functions as a prominent regulator for processes such as transcription and gene regulation, neuronal cell growth and differentiation, motility and axonal development and even neuronal cell death (Berridge et al, 2003; Bollimuntha et al, 2011; Sun et al, 2015). Thus, it is not surprising that disruption of Ca 2+ homeostasis in neuronal cells results in decreased neuronal functions leading to neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s (Albers and Beal, 2000; Bollimuntha et al, 2005; Cali et al, 2011; O’Bryant et al, 2009; Racette et al, 2006; Reboreda et al, 2011; Ruat and Traiffort, 2013; Zuccato and Cattaneo, 2007, 2009).…”