The Role of CALHM1 in Health and Disease

Dear Colleagues,

The large-pore channel CALHM1 (calcium homeostasis modulator 1) has been the subject of extensive studies in recent years due to its unconventional and pleiotropic role in ion and large molecule permeation (e.g., ATP). Its involvement in neuronal Ca²⁺ signaling and neuronal function, as well as in the conduction of sweet, bitter, and umami taste signals has revealed new fields of investigation. Strong evidence also supports the notion that CALHM1 is involved in pathologies such as Alzheimer's disease, ictus, epilepsy, or obesity.

In this scenario, we want to delve into the current knowledge of molecular and cellular aspects in which CALHM1 is involved in both physiological and pathological processes, and to address the need to find appropriate pharmacological strategies aimed at modulating CALHM1 in order to treat different diseases.

CALHM1 is expressed in all brain regions and neuronal cells, at the ER and plasma membranes. In neurons, CALHM1 generates Ca²⁺‐selective cation currents at the plasma membrane. It has also been shown to form a novel Ca²⁺‐permeable ion channel, whose gating is allosterically regulated by both membrane voltage and extracellular Ca²⁺ concentration. CALHM1 is also expressed in lingual type II taste cells, where it acts as a voltage-gated ATP-permeable large-pore channel that is required for neurotransmission from, and perception by, sweet-, umami-, and bitter-sensing taste cells.

Abnormal cellular Ca²⁺ homeostasis has been implicated in various neurodegenerative diseases, including Alzheimer’s disease. Ca²⁺ plays a critical role in cellular health, such that mild elevations of the cytosolic concentrations of free Ca²⁺ ions ([Ca²⁺]c) control neuronal signaling and neuronal excitability and plasticity, while high and uncontrolled [Ca²⁺]c elevations can cause neurotoxicity. Thus, alterations of Ca2+ homeostatic mechanisms are associated with neurodegeneration.

Focusing on one hand on the physiological role of CALHM1 in signal transduction in neurons and taste cells, and on the other hand on the role of CALHM1 in neurodegenerative diseases and ictus, the main scope of this Special Issue is to give an overview of our current understanding of CALHM1 pathophysiology and of the possible opportunities of targeting this novel channel to treat diseases.

Dr. Maria F. Cano-Abad
Dr. Philippe Marambaud
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• Neurodegenerative diseases 
• Ictus
• CALHM1
• Calcium homeostasis 
• ATP purinergic signaling 
• Epilepsy
• Metabolism 
• Mitochondria