Transient Receptor Potential Channels in Modulating Synaptic Plasticity and Cognitive Function: Potential Role of Pharmacological Agents.

Cognitive impairment represents the most prevalent complication of neurological diseases (NDs), which significantly affects the quality of life in affected patients. Current treatments primarily target neurotransmitter imbalances but do not act on the key pathological events such as Ca2+ dyshomeostasis, oxidative stress, microglia activation, mitochondrial dysfunction and neuroinflammation that occur in the brain of patients with NDs. Therefore, existing treatments fail to stop the progressive cognitive decline in these diseases. Thus, there is a critical need for literature which covers the potential novel therapeutic targets along with their modulators for the effective treatment of cognitive impairment associated with NDs. Recently, transient receptor potential (TRP) channels have emerged as key regulators of these pathological events implicated in ND-associated cognitive impairment. Many preclinical studies have demonstrated that pharmacological modulation of specific TRP channels can improve cognitive function in animal models of NDs. However, clinical translation of TRP channel modulators is still constrained due to a lack of subtype specificity, limited clinical data and difficulties in drug delivery across the blood-brain barrier (BBB). In the present review, we have discussed the structural diversity of TRP channels, their role in regulating synaptic plasticity and cognitive function, and their potential as pharmacological targets for the treatment of cognitive impairment, which can provide a direction for future research in this field.