Apoptosis, Neurotrophic Factors and Neurodegeneration

Abstract

Apoptosis is an active process of cell death characterized by distinct morphological features, and is often the end result of a genetic programme of events, i.e. programmed cell death (PCD). There is growing evidence supporting a role for apoptosis in some neurodegenerative diseases. This conclusion is based on DNA fragmentation studies and findings of increased levels of pro-apoptotic genes in human brain and in in vivo and in vitro model systems. Additionally, there is some evidence for a loss of neurotrophin support in neurodegenerative diseases. In Alzheimer's disease, in particular, there is strong evidence from human brain studies, transgenic models and in vitro models to suggest that the mode of nerve cell death is apoptotic. In this review we describe the evidence implicating apoptosis in neurodegenerative diseases with a particular emphasis on Alzheimer's disease.

The effects of intra-vestibular nucleus administration of brain-derived neurotrophic factor (BDNF) on recovery from peripheral vestibular damage in guinea pig

“…By what speci®c mechanism activation of p75 and/or trkB receptors might alter the expression of SN and YHT following UL is unknown at present. However, the high af®nity trkB receptors are linked via a transmembrane protein to tyrosine kinase, and receptor activation is thought to result in autophosphorylation of the tyrosine kinase domain and the activation of transcription factors which regulate gene expression [2,3]. Recent studies suggest that postsynaptic trkB receptors may be involved in tuning the af®nity and ef®cacy of the postsynaptic NMDA receptor [20], which is already implicated in the vestibular compensation process [21].…”

“…Neurotrophins (NTs) have been implicated in many forms of neuronal plasticity [2,3], and have been studied extensively in the peripheral vestibular system [4,5]; however, there are still few data available on NT expression and function in the VNC. NTs such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been identi®ed in the VNC [6±9], as have their low af®nity p75 receptors and high af®nity tyrosine kinase (trk) receptors [10±12].…”

NAP Enhances Neurodevelopment of Newborn Apolipoprotein E-Deficient Mice Subjected to Hypoxia

“…Much research in the field of neuroprotection has been done with great interest in the potential of these molecules as therapeutic agents (Dragunow et al, 1997;Lapchak, 1998;Zhao and Schwartz, 1998).…”

Qualitative and quantitative estimates of apoptosis from birth to senescence in the rat brain

“…43 Mid-gestational exposure to chlorpyrifos, a cholinesterase-inhibiting pesticide, produced changes in proliferation, migration, and apoptosis in rat neuroepithelium. 44 Apoptosis is believed to underlie the pathogenesis of a number of human neurodegenerative diseases, including Alzheimer's disease (reviewed in 45,46 ), Huntington's disease, 47 Parkinson's disease, 48 and Down's syndrome. 49 In normal human development, cortical cell number is estimated to peak at 28 weeks of gestation, followed by a reduction in number by about 70% during the last quarter of prenatal development.…”