The Neurotrophins and Their Role in Alzheimers Disease

Abstract

Besides being essential for correct development of the vertebrate nervous system the neurotrophins also play a vital role in adult neuron survival, maintenance and regeneration. In addition they are implicated in the pathogenesis of certain neurodegenerative diseases, and may even provide a therapeutic solution for some. In particular there have been a number of studies on the involvement of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in the development of Alzheimer’s disease. This disease is of growing concern as longevity increases worldwide, with little treatment available at the moment to alleviate the condition. Memory loss is one of the earliest symptoms associated with Alzheimer’s disease. The brain regions first affected by pathology include the hippocampus, and also the entorhinal cortex and basal cholinergic nuclei which project to the hippocampus; importantly, all these areas are required for memory formation. Both NGF and BDNF are affected early in the disease and this is thought to initiate a cascade of events which exacerbates pathology and leads to the symptoms of dementia. This review briefly describes the pathology, symptoms and molecular processes associated with Alzheimer’s disease; it discusses the involvement of the neurotrophins, particularly NGF and BDNF, and their receptors, with changes in BDNF considered particularly in the light of its importance in synaptic plasticity. In addition, the possibilities of neurotrophin-based therapeutics are evaluated.

7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome

“…Parallel with spatial memory, our data also indicated that 7, 8-DHF had a positive effect on fear memory deficits in Fmr1 KO mice. This finding largely confirms and extends previous findings of impaired spatial and fear memory in FXS mutant (Zhao et al, 2005;D'Hooge et al, 1997), and is also consistent with the rapidly growing literature on the positive effects of BDNF-based strategies for treating rodent models of memory loss (Allen et al, 2011;Leal et al, 2014). Notably, 7, 8-DHF had no effect on behavioral test performance in WT mice, which suggested that it has FXS-specific correcting effect on abnormal behaviors.…”

ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation

“…Loss of BDNF-PIV-driven expression causes a deficit in functioning of GABAergic interneurons in hippocampus and frontal cortex (Sakata et al, 2009;Sakata and Duke, 2014). BDNF exons I, II, and IV are downregulated in the AD brain (Allen et al, 2011). Despite resistance of GABAergic system to neurodegeneration, GABAergic currents show an agedependent reduction in AD brain (Rissman et al, 2007;Rissman and Mobley, 2011;Limon et al, 2012).…”

CREB expression mediates amyloid β-induced basal BDNF downregulation

“…Specifically, brain-derived neurotrophic factor (BDNF) is critical for survival of the neurons that degenerate in AD, for synaptic plasticity, and for memory consolidation (Allen et al, 2011;Fahnestock, 2011;Lu, 2003). BDNF messenger RNA (mRNA) (Connor et al, 1997;Garzon et al, 2002;Holsinger et al, 2000;Phillips et al, 1991) and protein (Ferrer et al, 1999;Hock et al, 2000;Michalski and Fahnestock, 2003;Peng et al, 2005) are decreased in AD.…”