Abstract
Neurodegenerative disorders (NDs) are heterogeneous groups of ailments typically characterized by progressive damage of the nervous system. Several drugs are used to treat NDs but they have only symptomatic benefits with various side effects. Numerous researches have been performed to prove the advantages of phytochemicals for the treatment of NDs. Furthermore, phytochemicals such as polyphenols might play a pivotal role in rescue from neurodegeneration due to their various effects as anti-inflammatory, antioxidative, and antiamyloidogenic agents by controlling apoptotic factors, neurotrophic factors (NTFs), free radical scavenging system, and mitochondrial stress. On the other hand, neurotrophins (NTs) including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT4/5, and NT3 might have a crucial neuroprotective role, and their diminution triggers the development of the NDs. Polyphenols can interfere directly with intracellular signaling molecules to alter brain activity. Several natural products also improve the biosynthesis of endogenous genes encoding antiapoptotic Bcl-2 as well as NTFs such as glial cell and brain-derived NTFs. Various epidemiological studies have demonstrated that the initiation of these genes could play an essential role in the neuroprotective function of dietary compounds. Hence, targeting NTs might represent a promising approach for the management of NDs. In this review, we focus on the natural product-mediated neurotrophic signal-modulating cascades, which are involved in the neuroprotective effects.
Highlights
Neurodegenerative disorders (NDs) are global health burdens that result from the progressive defect of neural cells, leading to dysfunction in the nervous system [1, 2]
We present the natural products that can modulate the neurotrophic signals to treat NDs
Zhang et al [135] found that chronic curcumin treatments activate extracellular signal-regulated kinases (ERK) or N-methyl-D-aspartate-cAMP response element-binding (CREB) signaling, accelerate the expression of brain-derived neurotrophic factor (BDNF), and enhance pathological, biochemical, and behavioral changes in an Alzheimer’s disease (AD) rat model induced by ventricular inoculation of Aβ1-42
Summary
Neurodegenerative disorders (NDs) are global health burdens that result from the progressive defect of neural cells, leading to dysfunction in the nervous system [1, 2]. Several NTFs including BDNF, NT-3, NGF, NT 4/5, bFGF-2, and erythropoietin (EPO) prevent neurons from injury They are capable of restoring NDs by interacting with the Trk receptor and enhancing the growth, survival, and regulation of neurons [33]. NT binding causes the initiation of the Trk receptor, triggering oligomerization and transautophosphorylation of the tyrosine moiety in the intracellular domain This event subsequently leads to the initiation of signaling transduction inside the cell through stimulation of the Ras/mitogen-activated protein kinase (MAPK) pathway resulting in CREB-dependent NT secretion and expression of Bcl-2, which enhances cell survival, development, and proliferation [45]. Selegiline enhances NGF formation and protects neurons from excitotoxicity and ischemia in the central nervous system [57]
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