Calpain

Calpains are a family of calcium-dependent cysteine proteases found in eukaryotes. They are involved in a wide range of cellular processes, including muscle contraction, cell proliferation, apoptosis, and signal transduction. Calpains are activated by an increase in intracellular calcium concentration, which binds to regulatory subunits of the enzyme. This binding event triggers a conformational change that exposes the active site, allowing the calpain to cleave its target proteins.

There are numerous calpain isoforms in mammals, with the most well-studied being calpain 1 and calpain 2. These canonical calpains are heterodimers, each composed of a large catalytic subunit and a small regulatory subunit. The catalytic subunit contains the active site responsible for proteolysis, while the regulatory subunit contains calcium-binding domains that mediate enzyme activation. Different calpain isoforms exhibit distinct tissue expression patterns and substrate specificities, contributing to their diverse cellular roles.

Dysregulation of calpain activity has been implicated in various pathological conditions, including neurodegenerative diseases, muscular dystrophies, and cancer. For example, excessive calpain activation can lead to the degradation of essential cellular components, contributing to cell death and tissue damage. Conversely, impaired calpain function can disrupt normal cellular processes, also leading to disease. Therefore, calpains represent important therapeutic targets, and inhibitors of calpain activity are being investigated for the treatment of a range of disorders.