Brain-Derived Neurotropic Factor in Neurodegenerative Disorders

Abstract

Globally, neurodegenerative diseases cause a significant degree of disability and distress. Brain-derived neurotrophic factor (BDNF), primarily found in the brain, has a substantial role in the development and maintenance of various nerve roles and is associated with the family of neurotrophins, including neuronal growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). BDNF has affinity with tropomyosin receptor kinase B (TrKB), which is found in the brain in large amounts and is expressed in several cells. Several studies have shown that decrease in BDNF causes an imbalance in neuronal functioning and survival. Moreover, BDNF has several important roles, such as improving synaptic plasticity and contributing to long-lasting memory formation. BDNF has been linked to the pathology of the most common neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. This review aims to describe recent efforts to understand the connection between the level of BDNF and neurodegenerative diseases. Several studies have shown that a high level of BDNF is associated with a lower risk for developing a neurodegenerative disease.

Keywords: Alzheimer’s disease; Parkinson’s disease; brain-derived neurotrophic factor; neurodegenerative disorders; tropomyosin receptor kinase B.

Figure 1

The figure shows the pathways by which BDNF signals can promote the survival of neuronal cells. The binding of BDNF to TrkB receptor switches on 3 different signaling pathways: the first pathway is the activation of the (PLC-γ) pathway which increases the level of Ca²⁺ that will terminate the apoptosis that is caused by inflammatory mediators (dashed lines), achieved by inhibiting the glycogen synthase kinase 3-beta (GSK-3β). The second pathway is activation of mTOR-dependent translation through the (PI3K) pathway, resulting in the transcription of BDNF mRNA. Additionally, the induction of Akt and Erk downstream enhances gene regulation through the NF-κB and CREB transcription factors. The third pathway is regulated by several factors such as zinc, epidermal growth factor, glucocorticoids, and the so called neurotrophic pathway, which is considered to be independent for BDNF as it can transactivate the TrkB and has a role in its signaling. This figure is adapted after modification from open access [10].

Figure 2

This figure is adapted after modification from open access [132]. The figure shows that ER stress will induce neuronal apoptosis by suppression of cyclin D1, activation of GSK3, and inhibition of Akt signaling from the BDNF/TrkB. A syn aggregation can decrease the expression of the TrkB receptor which will further result in loss of neurons.