Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer’s Disease

Version 1 : Received: 2 September 2023 / Approved: 4 September 2023 / Online: 5 September 2023 (03:45:49 CEST)

A peer-reviewed article of this Preprint also exists.

Jaberi, S.; Fahnestock, M. Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer’s Disease. Biomolecules 2023, 13, 1577. Jaberi, S.; Fahnestock, M. Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer’s Disease. Biomolecules 2023, 13, 1577.

Abstract

Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, and neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer’s disease (AD). Extracellular aggregates of amyloid-β (Aβ) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated Aβ and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on mechanisms behind exercise induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer’s disease pathology. Mechanisms include elevations in peripheral BDNF-inducing hormones such as osteocalcin, FNDC5/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are unclear but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline.

Keywords

Brain-derived neurotrophic factor (BDNF); Alzheimer’s disease; exercise; osteocalcin; FNDC5/irisin; lactate; APP processing; dementia; cognition; learning and memory

Subject

Biology and Life Sciences, Neuroscience and Neurology

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