Challenges of BDNF-based therapies: From common to rare diseases

Miranda-Lourenço, Catarina; Ribeiro-Rodrigues, Leonor; Fonseca-Gomes, João; Tanqueiro, Sara R.; Belo, Rita F.; Ferreira, Catarina; Rei, Nádia; Ferreira-Manso, Mafalda; Almeida-Borlido, Carolina de; Costa-Coelho, Tiago; Freitas, Céline Felicidade; Zavalko, Svitlana; Mouro, Francisco; Sebastião, Ana M.; Xapelli, Sara; Rodrigues, Tiago M.; Diógenes, Maria José

doi:10.1016/j.phrs.2020.105281

Cited by 44 publications

(20 citation statements)

References 233 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistently, a decrease in BDNF levels has been reported in neurodegenerative disorders, such as AD [69,71], Huntington's disease (HD) [72], and epilepsy [73], and recent strategies aimed at sustaining or even amplifying the production of BDNF have been proved to be beneficial in patients with HD [74], AD [75,76], Parkinson's disease (PD) [77,78], amyotrophic lateral sclerosis (ALS) [79][80][81], stroke [82][83][84], and spinal cord injury [85][86][87][88]. However, it is worth mentioning that despite the extensive literature dating back to the early 1990s, in which reduced BDNF levels in the brain have been associated with neurodegenerative diseases, only in patients with HD has a genetic defect in BDNF gene been mechanistically related to the pathology [89].…”

Section: Bdnf In Health and Diseasementioning

confidence: 84%

See 1 more Smart Citation

Putting Cells in Motion: Advantages of Endogenous Boosting of BDNF Production

Brattico

Bonetti

Ferretti

et al. 2021

Cells

View full text Add to dashboard Cite

Motor exercise, such as sport or musical activities, helps with a plethora of diseases by modulating brain functions in neocortical and subcortical regions, resulting in behavioural changes related to mood regulation, well-being, memory, and even cognitive preservation in aging and neurodegenerative diseases. Although evidence is accumulating on the systemic neural mechanisms mediating these brain effects, the specific mechanisms by which exercise acts upon the cellular level are still under investigation. This is particularly the case for music training, a much less studied instance of motor exercise than sport. With regards to sport, consistent neurobiological research has focused on the brain-derived neurotrophic factor (BDNF), an essential player in the central nervous system. BDNF stimulates the growth and differentiation of neurons and synapses. It thrives in the hippocampus, the cortex, and the basal forebrain, which are the areas vital for memory, learning, and higher cognitive functions. Animal models and neurocognitive experiments on human athletes converge in demonstrating that physical exercise reliably boosts BDNF levels. In this review, we highlight comparable early findings obtained with animal models and elderly humans exposed to musical stimulation, showing how perceptual exposure to music might affect BDNF release, similar to what has been observed for sport. We subsequently propose a novel hypothesis that relates the neuroplastic changes in the human brains after musical training to genetically- and exercise-driven BDNF levels.

show abstract

Section: Bdnf In Health and Diseasementioning

confidence: 84%

“…In an attempt to increase BDNF permeability through the BBB, intranasal delivery in animal models was proposed [75,122,123]. However, the reduced permeability of the nasal mucus limits the absorption efficiency [79].…”

Section: Figurementioning

confidence: 99%

Putting Cells in Motion: Advantages of Endogenous Boosting of BDNF Production

Brattico

Bonetti

Ferretti

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…To date, the search for small molecule agonists has been mainly unsuccessful, or questionable at best ( Todd et al, 2014 ; Boltaev et al, 2017 ; Pankiewicz et al, 2021 ). The delivery of BDNF has universally failed as a therapeutic agent probably due to its inability to cross the BBB, the short half-life, and the difficulties of delivery to specific brain areas in a precise spatio-temporal fashion ( Miranda-Lourenco et al, 2020 ). A variety of approaches are currently being pursued to address the issue of BDNF delivery, including the use of biomaterials and nanoparticles, viral mediated gene delivery and transplantation of neurotrophin-producing cells ( Houlton et al, 2019 ; Jarrin et al, 2021 ).…”

Section: Therapeutic Relevance and Future Perspectivementioning

confidence: 99%

TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions

Tessarollo

Yanpallewar

2022

Front. Neurosci.

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of secreted growth factors and binds with high affinity to the TrkB tyrosine kinase receptors. BDNF is a critical player in the development of the central (CNS) and peripheral (PNS) nervous system of vertebrates and its strong pro-survival function on neurons has attracted great interest as a potential therapeutic target for the management of neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), Huntington, Parkinson’s and Alzheimer’s disease. The TrkB gene, in addition to the full-length receptor, encodes a number of isoforms, including some lacking the catalytic tyrosine kinase domain. Importantly, one of these truncated isoforms, namely TrkB.T1, is the most widely expressed TrkB receptor in the adult suggesting an important role in the regulation of BDNF signaling. Although some progress has been made, the mechanism of TrkB.T1 function is still largely unknown. Here we critically review the current knowledge on TrkB.T1 distribution and functions that may be helpful to our understanding of how it regulates and participates in BDNF signaling in normal physiological and pathological conditions.

show abstract

“…The role of BDNF has been received significant attention. I refer the reader to several past reviews (Autry and Monteggia, 2012;Katz, 2014;Li and Pozzo-Miller, 2014;Miranda-Lourenço et al, 2020). Furthermore, an inward rectifying K + channel Kir4.1 that functions to maintain normal extracellular K + levels is important for neuronal excitability (Della Vecchia et al, 2021).…”

Section: Critical Elements That Contribute To Excitation/inhibition I...mentioning

confidence: 99%

Excitation and Inhibition Imbalance in Rett Syndrome

2022

Front. Neurosci.

View full text Add to dashboard Cite

A loss of the excitation/inhibition (E/I) balance in the neural circuit has emerged as a common neuropathological feature in many neurodevelopmental disorders. Rett syndrome (RTT), a prevalent neurodevelopmental disorder that affects 1:10,000–15,000 women globally, is caused by loss-of-function mutations in the Methyl-CpG-binding Protein-2 (Mecp2) gene. E/I imbalance is recognized as the leading cellular and synaptic hallmark that is fundamental to diverse RTT neurological symptoms, including stereotypic hand movements, impaired motor coordination, breathing irregularities, seizures, and learning/memory dysfunctions. E/I balance in RTT is not homogeneously altered but demonstrates brain region and cell type specificity instead. In this review, I elaborate on the current understanding of the loss of E/I balance in a range of brain areas at molecular and cellular levels. I further describe how the underlying cellular mechanisms contribute to the disturbance of the proper E/I ratio. Last, I discuss current pharmacologic innervations for RTT and their role in modifying the E/I balance.

show abstract

Challenges of BDNF-based therapies: From common to rare diseases

Cited by 44 publications

References 233 publications

Putting Cells in Motion: Advantages of Endogenous Boosting of BDNF Production

Putting Cells in Motion: Advantages of Endogenous Boosting of BDNF Production

TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions

Excitation and Inhibition Imbalance in Rett Syndrome

Contact Info

Product

Resources

About