Neurotrophin Receptor-Based Strategies for Alzheimers Disease

Frank   M.   Longo; Stephen   M.   Massa

doi:10.2174/1567205053585819

Abstract

The traditional perspective of applying neurotrophins in the context of Alzheimers disease is based on the premise that neurotrophins are capable of upregulating cholinergic function and of rendering neurons less vulnerable to certain processes causing degeneration. Factors limiting the therapeutic application of neurotrophin proteins include their poor pharmacological properties and their pleiotropic effects mediated by interaction with Trk, p75NTR and sortilin receptors. Recent studies suggesting and that pro-forms of neurotrophins accumulating in Alzheimers and other pathological states cause cell death, that p75NTR modulates amyloid beta- and injury-induced neurodegeneration and that small molecules can be created that bind specifically to individual neurotrophin receptors point to novel strategies by which neurotrophin receptors might be targeted in Alzheimers and other neuropathological states.

Keywords: neurotrophin, trk tyrosine kinase receptors, protein kinase c (pkc), neuropathies, schwann cell hypertrophy, expression, ngf loop, antisense, neuroprotection