Abstract
Neurotrophins are a collection of structurally and functionally related proteins. They play important roles in many aspects of neural development, survival, and plasticity. Traumatic brain injury (TBI) leads to different levels of central nervous tissue destruction and cellular repair through various compensatory mechanisms promoted by the injured brain. Many studies have shown that neurotrophins are key modulators of neuroinflammation, apoptosis, blood–brain barrier permeability, memory capacity, and neurite regeneration. The expression of neurotrophins following TBI is affected by the severity of injury, genetic polymorphism, and different post-traumatic time points. Emerging research is focused on the potential therapeutic applications of neurotrophins in managing TBI. We conducted a comprehensive review by organizing the studies that demonstrate the role of neurotrophins in the management of TBI.
Highlights
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We will primarily focus on the characteristics of the four neurotrophins in the human body: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4), sometimes known as neurotrophin 5 (NT-5) (NT-4/5) [6]
Individual neurotrophins activate corresponding tropomyosin receptor kinase (Trk) receptors with high specificity and affinity, with NGF binding to TrkA, BDNF and NT-4/5 binding to TrkB, and NT-3 binding to TrkC [8,9,10]
Summary
Neurotrophins are a collection of structurally and functionally related proteins. They undergo proteolytic processes from proneurotrophins (precursor proteins) that possess a Cterminal mature domain and an N-terminal prodomain [1]. The prodomains ensure proper protein folding and dimerization, whereas the mature domains play a role in the biological effects of neurotrophins [2] They were first discovered as physiological regulators of the sympathetic and sensory neurons that modulate neuronal survival, function, and development within the peripheral nervous system (PNS) and in the central nervous system (CNS) [3]. P75NTR, the pan-neurotrophin receptor, plays various complex roles in regulating cell survival, neurodegeneration, and cell death It initiates pro-apoptotic cascades through different signaling pathways [22], including the nuclear factor (NF)-κB pathway, the Jun kinase pathway, and the activity of Rho, which participate in neuronal survival, apoptosis, and growth cone motility, respectively [8,19]. P75NTR can activate the Akt pathway, which plays an important role in the Trk-mediated neurotrophic signaling pathway, to support the pro-survival function, contrary to the popular hypothesis that p75NTR is only responsible for neuronal cell apoptosis [4,30]
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