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J Pharmacol Ther Res 2017 Volume 1 Issue 2

November 02-03, 2017 Chicago, USA

International Congress on

International Conference and Exhibition on

Drug Discovery, Designing and Development

Biochemistry, Molecular Biology: R&D

Small molecule pro-neurotrophic therapeutic activity in murine models of Alzheimer’s disease

Stuart Maudsley

University of Antwerp, Belgium

ge-related neurodegenerative diseases, such as Alzheimer’s

disease, will represent one of the largest future burdens on

worldwide healthcare systems due to the increasing proportion

of elderly in our society. As deficiencies in neurotrophins

are implicated in the pathogenesis of many age-related

neurodegenerative disorders, it is reasonable to consider

that global neurotrophin resistance may also become a major

healthcare threat. Central nervous system networks are

effectively maintained through aging by neuroprotective and

neuroplasticity signaling mechanisms which are predominantly

controlled by neurotrophin receptor signaling. Neurotrophin

receptors are single pass receptor tyrosine kinases that form

dimeric structures upon ligand binding to initiate cellular

signaling events that control many protective and plasticity-

related pathways. Declining functionality of the neurotrophin

ligand–receptor system is considered one of the hallmarks of

neuropathological aging. Therefore, it is imperative to develop

effective therapeutic strategies to contend with this significant

issue. The development of nonpeptidergic, small-molecule

ligands can overcome these limitations, and productively

regulate this important receptor system with beneficial effects.

We have found that in multiple models of Alzheimer’s disease

the previously employed anti-depressant Elavil can exert potent

pro-neurotrophic activity through a series of complementary

mechanisms. This small molecular agent possesses the capacity

to significantly enhance cognitive performance in mouse

models possessing considerable levels of dementia and amyloid

pathology. In this respect agents such as Elavil may represent

an important addition to a new wave of therapeutic strategies

against dementia.