title: Deciphering proneurotrophin actions.
abstract: Like most growth factors, neurotrophins are initially synthesized as precursors that are cleaved to release C-terminal mature forms. The well-characterized mature neurotrophins bind to Trk receptors to initiate survival and differentiative responses. More recently, the precursor forms or proneurotrophins have been found to act as distinct ligands by binding to an unrelated receptor complex consisting of the p75 neurotrophin receptor (p75) and sortilin to initiate cell death. Induction of proNGF and p75 has been observed in preclinical injury models and in pathological states in the central nervous system, and strategies that block the proNGF/p75 interaction are effective in limiting neuronal apoptosis. In contrast, the mechanisms that regulate expression of other proneurotrophins, including proBDNF and proNT-3, are less well understood. Here, recent findings on the biological actions, regulation of expression, and pathophysiological effects of proneurotrophins will be reviewed.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Room C610, 1300 York Ave, New York, NY, 10065, USA, blhempst@med.cornell.edu.
authors.forename: B L
authors.initials: BL
authors.lastname: Hempstead
mesh_terms: D000375:Aging; D000818:Animals; D006801:Humans; D020932:Nerve Growth Factor / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology*; D009473:Neuronal Plasticity; D011498:Protein Precursors / Q000502:physiology*; D013570:Synaptic Membranes / Q000502:physiology
chemical_list: D009414:Nerve Growth Factors; D011498:Protein Precursors; C061397:pro-nerve growth factor, human; D020932:Nerve Growth Factor