Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases.

摘要: No drug has been approved to prevent neuronal cell loss in patients suffering from Parkinson's disease (PD) or Alzheimer's (AD); despite increased comprehension of the underlying molecular causes, therapies target cognitive functional improvement and motor fluctuation control. Drug design strategies that adopt "one protein, one target" philosophy fail address multifactorial aetiologies neurodegenerative disorders such as AD PD optimally. On contrary, restoring neurotransmitter levels by combined combinatorial inhibition cholinesterases, monoamine oxidases, adenosine A2A A receptors, conjunction with counter oxidative stress beta-amyloid plaque accumulation, would constitute a therapeutically robust, multitarget approach. This extensive review delineates therapeutic advantages combining dual-acting molecules inhibit oxidases cholinesterases and/or describes structure-activity relationships compound classes include, but are not limited to, alkaloids, coumarins, chalcones, donepezil-propargylamine conjugates, homoisoflavonoids, resveratrol analogs, hydrazones, pyrazolines. In wake recent advances network biology, silico approaches, omics, this emphasizes need consider conceptually informed research for discovery, context mounting burden posed chronic diseases complex pathophysiologies involving multiple signalling pathways numerous targets.