Recent Advances on the Role of Brain-Derived Neurotrophic Factor (BDNF) in Neurodegenerative Diseases

Abstract

Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are essential for neuronal survival and growth. The signaling cascades initiated by BDNF and its receptor are the key regulators of synaptic plasticity, which plays important role in learning and memory formation. Changes in BDNF levels and signaling pathways have been identified in several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, and have been linked with the symptoms and course of these diseases. This review summarizes the current understanding of the role of BDNF in several neurodegenerative diseases, as well as the underlying molecular mechanism. The therapeutic potential of BDNF treatment is also discussed, in the hope of discovering new avenues for the treatment of neurodegenerative diseases.

Distinct neuroinflammatory signatures exist across genetic and sporadic ALS cohorts

“…BDNF expression has also been shown to correlate with decreased cognition 64 . Importantly, many preclinical studies investigating the effects of BDNF in ALS are biased toward SOD1 mouse models 65,66 , in which increased BDNF-TrkB is observed 67 . Further, a phase III clinical trial conducted using recombinant methionyl human BDNF did not demonstrate therapeutic benefit, though this study and further trials conducted thereafter did not stratify genetically; importantly, C9orf72 mutations in ALS had not been discovered at the time 68,69 .…”

Mechanisms of chemotherapy-related cognitive impairment

“…Do śmierci komórek może także dochodzić na drodze blokowania drogi PI3K/AKT przez homolog fosfatazy i tensyny (phosphatase and tensin homolog -PTEN), która jest niezbędna do potencjalizacji indukowanej TrkB. Także każde zaburzenie w szlaku BDNF/TrkB skutkuje nieprawidłowościami w szlakach sygnałowych, wzrostem cytokin zapalnych, zaburzeniami plastyczności synaptycznej, co może być podłożem chemobrain [107,108].…”

Methylation of BDNF gene in association with episodic memory in women

“…Throughout life, the brain-derived neurotrophic factor (BDNF) plays an important role in neural development and synaptic plasticity in learning and memory (reviewed by Day and Sweatt, 2010 ; Silakarma and Sudewi, 2019 ; Azman and Zakaria, 2022 ). The BDNF gene is a member of the neurotrophin family that is highly expressed in the central nervous system (CNS) and has impacts on many brain and body functions.…”

“…Recent studies have suggested that the dysregulation of BDNF contributes to the pathogenesis of several major diseases and disorders, such as Huntington's disease, Alzheimer's disease, and depression (reviewed by Zheleznyakova et al, 2016 ), especially mediated by epigenetic processes. Some studies show that BDNF methylation CpG regions have been linked to cognitive deficits and psychiatric diseases (Grayson and Guidotti, 2013 ; Azman and Zakaria, 2022 ).…”

“…Recent studies have suggested that the dysregulation of BDNF contributes to the pathogenesis of several major diseases and disorders, such as Huntington's disease, Alzheimer's disease, and depression (reviewed by Zheleznyakova et al, 2016), especially mediated by epigenetic processes. Some studies show that BDNF methylation CpG regions have been linked to cognitive deficits and psychiatric diseases (Grayson and Guidotti, 2013;Azman and Zakaria, 2022). Moreover, differences are observed in the methylation level at CpG sites of BNDF promoter IV on poor performance in learning and memory tasks such as the Brief Visuospatial Memory Test-Revised (BVMT-R) (Engelmann et al, 2020) and the Rey Complex Figure Test (RCFT) in women with major depressive disorders (MDDs) (Ferrer et al, 2019).…”