Transient receptor potential melastatin 2 (TRPM2) (TRPM2)

Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that functions as a key sensor for oxidative stress in various tissues, including the brain, heart, and immune system [3, 6]. It is uniquely activated by ADP-ribose (ADPR), a metabolite generated in response to reactive oxygen species (ROS) and DNA damage, which binds to the channel's C-terminal NUDT9-H domain [7, 12]. Activation of TRPM2 leads to an influx of calcium ions, which subsequently triggers downstream signaling cascades, most notably the c-Jun N-terminal kinase (JNK) pathway [1, 2]. This TRPM2/JNK axis is a critical mediator of oxidative stress-induced cellular outcomes, such as apoptosis, autophagy, and the production of inflammatory cytokines [2, 10]. In pathological contexts, the pathway is implicated in neurodegenerative diseases, ischemic stroke, and several cancers, where it can either promote cell death or support tumor cell survival and chemoresistance [4, 10, 13]. Consequently, TRPM2 is considered a promising therapeutic target, with research exploring small-molecule inhibitors like ACA and peptide-based modulators to treat conditions characterized by oxidative damage [11, 13].

Other names

LTRPC2TRPC7KNP3NUDT9L1

TRPM2 is a non-selective cation channel activated by ADP-ribose (ADPR) and calcium. Under oxidative stress, ADPR is generated (often via PARP/PARG activity), which binds to the C-terminal NUDT9-H domain of TRPM2, causing channel opening and calcium influx. This influx activates downstream kinases like JNK, leading to various cellular outcomes such as apoptosis or autophagy.