Alzheimer's disease, enzyme targets and drug discovery struggles: From natural products to drug prototypes

作者：Silva Tiago; Reis Joana; Teixeira Jose; Borges Fernanda^*

来源：Ageing Research Reviews, 2014, 15: 116-145.

DOI：10.1016/j.arr.2014.03.008

• Alzheimer's disease
• Acetylcholinesterase and inhibitors
• beta- and gamma-secretases and inhibitors
• Sirtuins and inhibitors
• Caspases and inhibitors
• Glycogen synthase kinase-3 and inhibitors
• Autophagy enhancers
• Synaptogenesis enhancers

Alzheimer's disease (AD) is an incapacitating neurodegenerative disease that slowly destroys brain cells. This disease progressively compromises both memory and cognition, culminating in a state of full dependence and dementia. Currently, AD is the main cause of dementia in the elderly and its prevalence in the developed world is increasing rapidly. Classic drugs, such as acetylcholinesterase inhibitors (AChEIs), fail to decline disease progression and display several side effects that reduce patient's adhesion to pharmacotherapy. The past decade has witnessed an increasing focus on the search for novel AChEIs and new putative enzymatic targets for AD, like beta- and gamma-secretases, sirtuins, caspase proteins and glycogen synthase kinase-3 (GSK-3). In addition, new mechanistic rationales for drug discovery in AD that include autophagy and synaptogenesis have been discovered. Herein, we describe the state-of-the-art of the development of recent enzymatic inhibitors and enhancers with therapeutic potential on the treatment of AD.

• 出版日期2014-5