Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential

Abstract

Synaptic abnormalities are a cardinal feature of Alzheimer’s disease (AD) that are known to arise as the disease progresses. A growing body of evidence suggests that pathological alterations to neuronal circuits and synapses may provide a mechanistic link between amyloid β (Aβ) and tau pathology and thus may serve as an obligatory relay of the cognitive impairment in AD. Brain-derived neurotrophic factors (BDNFs) play an important role in maintaining synaptic plasticity in learning and memory. Considering AD as a synaptic disorder, BDNF has attracted increasing attention as a potential diagnostic biomarker and a therapeutical molecule for AD. Although depletion of BDNF has been linked with Aβ accumulation, tau phosphorylation, neuroinflammation and neuronal apoptosis, the exact mechanisms underlying the effect of impaired BDNF signaling on AD are still unknown. Here, we present an overview of how BDNF genomic structure is connected to factors that regulate BDNF signaling. We then discuss the role of BDNF in AD and the potential of BDNF-targeting therapeutics for AD.

Effects of Aerobic Training on Brain Plasticity in Patients with Mild Cognitive Impairment: A Systematic Review of Randomized Controlled Trials

“…BDNF plays an essential role in maintaining synaptic plasticity in learning and memory. BDNF plays a vital role in facilitating nerve growth and maturation through the developmental stages and the regulation of synaptic transmission and flexibility in adulthood [ 37 , 38 ]. BDNF is mainly synthesized in neurons and glial cells and is then transported to presynaptic terminals and postsynaptic dendrites in the brain.…”

“…In addition, BDNF/TrkB generates many downstream intracellular signaling pathways, such as mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK), PI3K, and phospholipase Cγ/protein kinase C (PLCγ/PKC) These signaling pathways are associated with the activation of the CREB transcription factor, which mediates the transcription of genes essential for synaptic plasticity [ 44 ]. Under pathological conditions such as AD, BDNF is involved in Aβ accumulation, tau phosphorylation, the neuroinflammatory response, and apoptosis [ 37 ]. In particular, Aβ has been shown to disrupt BDNF processing both activity-dependently and activity-independently [ 37 ].…”

“…Under pathological conditions such as AD, BDNF is involved in Aβ accumulation, tau phosphorylation, the neuroinflammatory response, and apoptosis [ 37 ]. In particular, Aβ has been shown to disrupt BDNF processing both activity-dependently and activity-independently [ 37 ]. Recent studies have shown that there is a positive relationship between PA and the concentration of neurotrophic factor in different parts of the body, such as the brain, blood, and muscles [ 45 , 46 , 47 , 48 ].…”

The emerging role of furin in neurodegenerative and neuropsychiatric diseases

“…AD is a progressive neurodegenerative disease and the main cause of dementia in the elderly, affecting around 6% of the population over the age of 65 [ 223 ]. Currently, there is no effective prevention or treatment strategy for AD [ 20 , 224 , 225 ]. The major pathological hallmarks of AD are the accumulation of two aggregated proteins in the brain, Aβ and tau, leading to the formation of extracellular senile plaques and intracellular neurofibrillary tangles (NFTs), respectively [ 226 , 227 ].…”

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“…The use of DSP4 has certain disadvantages as the drug suppresses not only NA, but also other neuromodulators produced in the LC such as galanin or brain-derived neurotrophic factor (BDNF), which have also been implicated in AD [ 74 , 75 ]. Besides, the injury to neurons caused by DSP4 could itself promote inflammatory responses.…”