Natural Medicines and Their Underlying Mechanisms of Prevention and Recovery from Amyloid Β-Induced Axonal Degeneration in Alzheimer's Disease

In Alzheimer's disease (AD), amyloid beta (A beta) induces axonal degeneration, neuronal network disruption, and memory impairment. Although many candidate drugs to reduce A beta have been clinically investigated, they failed to recover the memory function in AD patients. Reportedly, A beta deposition occurred before the onset of AD. Once neuronal networks were disrupted by A beta, they could hardly be recovered. Therefore, we speculated that only removal of A beta was not enough for AD therapy, and prevention and recovery from neuronal network disruption were also needed. This review describes the challenges related to the condition of axons for AD therapy. We established novel in vitro models of A beta-induced axonal degeneration. Using these models, we found that several traditional medicines and their constituents prevented or helped recover from A beta-induced axonal degeneration. These drugs also prevented or helped recover from memory impairment in in vivo models of AD. One of these drugs ameliorated memory decline in AD patients in a clinical study. These results indicate that prevention and recovery from axonal degeneration are possible strategies for AD therapy.