Genomics and proteomics are changing discovery, development and clinical use of dementia drugs

Abstract

Drug discovery as well as the optimization of drug use in dementia is at the verge of a new stage, which is being brought about by the broad and systematic application of functional genomics and proteomics. Alzheimer’s disease is the focus of this transition, whereas vascular dementia can benefit from the spill over from cardiovascular research, which is already more developed. This review discusses the stratification of Alzheimer’s patients for cholinesterase inhibitor therapy according to genetic polymorphisms and the modulating roles of mutations in the genes coding for angiotensin-converting enzyme, presenilin, cathepsin and potassium channels, which are all hotbeds for ‘omics’ applications. Lastly, the case for humanin is discussed as an example of the discovery of a potentially novel neuroprotective pathway that could be exploited for dementia drugs.

Keywords::

• angiotensin-converting enzyme
• apolipoprotein E
• cathepsin
• cholinesterase inhibitors
• functional genomics
• humanin
• low-density lipoprotein receptor-related protein-associated protein
• neuronal nicotinic cholinergic receptors
• potassium channels
• presenilin
• proteomics
• soluble epoxide hydrolase