Tailoring MAPK Pathways: New Therapeutic Avenues for Treating Alzheimer's Disease

Alzheimer's disease (AD) is irreversible, progressive, and refractory in nature and is managed very poorly clinically due to very limited treatment outcomes. Unfortunately, most of the multiple clinical trials involving AD patients were unsuccessful in improving the disease prognosis. At the cellular level, many signaling pathways have been proposed to be involved in the sterile/refractory behavior of degenerating neurons in AD. Due to the involvement of p38MAPK in the pathogenesis of Alzheimer's disease, numerous investigations have attempted to determine the beneficial effects of MAPK targeting on memory, inflammatory programming of the brain, and synaptic plasticity. In view of this, various clinical trials involving several MAPK inhibitors (with good safety profiles and few side effects) have yielded positive results in AD patients, suggesting that MAPK targeting may be effective for reducing the pathogenesis of AD, but due to selectivity, dosing, and patient stratification, this aspect still needs further development. In view of their selectivity and off-target effects, only a few MAPK inhibitors have been employed in clinical trials against AD, indicating the scope of their development in this area. Therefore, this study focused on MAPK-based interventions as an upcoming and innovative approach for alleviating AD, with a special emphasis on clinical studies.