Neurotrophic fragments as therapeutic alternatives to ameliorate brain aging

Abstract

Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes. During this physiological process, the brain is the most affected organ due to changes in its structural and chemical functions, such as changes in plasticity and decrease in the number, diameter, length, and branching of dendrites and dendritic spines. Likewise, it presents a great reduction in volume resulting from the contraction of the gray matter. Consequently, aging can affect not only cognitive functions, including learning and memory, but also the quality of life of older people. As a result of the phenomena, various molecules with notable neuroprotective capacity have been proposed, which provide a therapeutic alternative for people under conditions of aging or some neurodegenerative diseases. It is important to indicate that in recent years the use of molecules with neurotrophic activity has shown interesting results when evaluated in in vivo models. This review aims to describe the neurotrophic potential of molecules such as resveratrol (3,5,4′-trihydroxystilbene), neurotrophins (brain-derived neurotrophic factor), and neurotrophic-type compounds such as the terminal carboxyl domain of the heavy chain of tetanus toxin, cerebrolysin, neuropeptide-12, and rapamycin. Most of these molecules have been evaluated by our research group. Studies suggest that these molecules exert an important therapeutic potential, restoring brain function in aging conditions or models of neurodegenerative diseases. Hence, our interest is in describing the current scientific evidence that supports the therapeutic potential of these molecules with active neurotrophic.

PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson’s disease in rats

“…PI3K/AKT cascading axis, via its impact on a plethora of proteins, has been established to be one of the most crucial pathways capable of ameliorating neuronal survival, improving neurogenesis, and repressing apoptosis induced by neurotoxins in PD models (Zheng et al 2021a , b ; Khezri and Ghasemnejad-Berenji 2022 ; Wang et al 2022 ). PI3K/AKT is activated after the binding of diverse neurotrophic factors to their membrane receptors including brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrKB) (Jin et al 2022 ; Gendy et al 2023 ) and silent information regulator type 1 (SIRT1)/insulin growth factor 1 (IGF1) cascading axes (Yang et al 2018 ; Flores et al 2023 ; Arjunan et al 2023 ).…”

Chronic resveratrol administration reduces oxidative stress and brain cell loss and improves memory of recognition in old rats

“…Human aging affects the entire organism; in particular, aging in the brain is manifested by a decrease in motor and cognitive functions, especially those related to executive abilities, attention processes, and learning and storage of new information (Laurence & Michel, 2017; Yuan & Cai, 2021). In the aged brain, there are a series of changes in its morphology that denote significant atrophy and a loss of brain tissue volume, in addition to biochemical modifications that exacerbate the processes of oxidation, inflammation, and apoptosis (Giudetti et al., 2018; Ionescu‐Tucker & Cotman, 2021), coupled with a low level of antioxidant protection and the production of neurotrophic molecules (Flores et al., 2023; Lange & Li, 2018).…”