Abstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive decline of cognitive and behavioral functions, with typical symptoms such as memory loss and language or problem-solving difficulties [1]
The neurotrophin homodimers interact with two distinct classes of receptors: p75 neurotrophin receptor (p75NTR), which is a member of the tumor necrosis receptor superfamily, and tropomyosin receptor kinase (Trk) (Figure 1) [63]
The exogenous administration of peptides derived from growth factors is an attractive therapeutic approach, given their roles in proliferation, differentiation, plasticity, and survival of neuronal cells
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive decline of cognitive and behavioral functions, with typical symptoms such as memory loss and language or problem-solving difficulties [1]. The neurofibrillary tangles are formed when the neuronal microtubule-associated protein tau is abnormally hyperphosphorylated by kinases such as glycogen synthase kinase 3β (GSK3β), leading to its release from the microtubule and intracellular aggregation into bundles of filaments [9] It causes neuronal dysfunctions such as axon integrity and vesicular transport impairment [9,10]. The “amyloid hypothesis” ( known as the amyloid cascade hypothesis) has been the mainstream explanation for the pathogenesis of AD for over 25 years, but is still a highly controversial topic in the field This hypothesis suggests that the accumulation and deposition of Aβ peptides is the initiating factor that triggers a cascade of diseasecausing processes such as tau-tangle formation, neuroinflammation, synapse dysfunction, and cell death, which leads to dementia [11]. These reports highlight the complexity and multifactorial nature of AD
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