Targeting neurotrophin receptors in the central nervous system.
Neurotrophic factors, and in particular the neurotrophins, restore the function of damaged neurons and prevent apoptosis in adults. The potential therapeutic property of the neurotrophins is however, complicated by the peptidergic structure of these trophic factors, which impairs their penetration into the brain parenchyma, and therefore makes their pharmaco-therapeutic properties difficult to evaluate. In this article we will focus on the neurotrophin Brain-derived neurotrophic factor (BDNF) and its receptors to address various therapeutic strategies that may overcome this problem. We will call this strategy "small molecule approach" because it relies on increasing the function of endogenous neurotrophins by pharmacological compounds that induce synthesis and release of neurotrophins in relevant brain areas or by small synthetic molecules that bind and activate specific neurotrophin receptors. The ability of small molecules to mimic BDNF has a potential therapeutic importance in preventing neuronal damage in several chronic neurodegenerative diseases including Parkinson's Disease, Alzheimer's Disease, and AIDS dementia.
Mocchetti
Italo
I
Department of Neuroscience, Georgetown University Medical Center, Washington DC 20057, USA. moccheti@georgetown.edu
Brown
Milton
M
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D005732:Gangliosides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D017475:Receptors, Nerve Growth Factor / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D005732:Gangliosides; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor