Zhao_2019_ACS.Chem.Neurosci_10_922

Alzheimer's disease (AD) has been a devastating neurodegenerative disorder and lacks effective treatment to improve the prognosis for patients. Symptomatic treatment for AD mainly includes two categories: Acetylcholinesterase inhibitors and the N-methyl-d-aspartate (NMDA) receptor antagonist (memantine). They cannot significantly improve the quality of life and extend survival time for AD patients. Worse, almost all clinical trials for disease-modifying drugs have failed, and the reduction of brain beta-amyloid (Abeta) deposition by multiple approaches, including inhibitors of beta- or gamma-secretase, vaccines, and antibodies against Abeta deposition, was found to have little effect on AD progression. A new therapeutic strategy for AD is urgently needed. Parkinson's disease also is a neurodegenerative disease having no effective treatment for modifying the disease. Nevertheless, successful symptomatic treatment using the combined therapies of l-DOPA supplement and modulators of l-DOPA metabolism greatly improves the prognosis for PD patients; the average survival time of the patient has been extended from 3-4 years to 10-15 years although dopaminergic neurons are still progressively decreasing. This provides useful implications for AD therapeutic strategies. AD patients manifest global cognitive decline, prominently represented by memory deficit, especially in the early stages of the disease. Further, the degree of decreased cognitive abilities correlates with cholinergic dysfunction and the hypometabolism of glucose, the dominant energy fuel for brain. Thus, the amelioration of brain cholinergic function and brain energy metabolism may be effective treatment to improve cognitive abilities of AD patients. Here, we highlighted the explorations of symptomatic therapeutics through modulating brain cholinergic function and energy metabolism in AD.