Delayed onset of inherited ALS by deletion of the BDNF receptor TrkB.T1 is non-cell autonomous

Yanpallewar, Sudhirkumar; Fulgenzi, Gianluca; Tomassoni-Ardori, Francesco; Barrick, Colleen; Tessarollo, Lino

doi:10.1016/j.expneurol.2020.113576

Cited by 18 publications

(15 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggestion was supported by experiments in which TrkB.T1 deletion in mutant SOD1 mice delays the onset of the disease, slows down the motoneuron loss and improves mobility test results at the end stage of the disease compared with normal mutant SOD1 mice. Although, the increase in TrkB.T1 could be secondary to the increased astrogliosis in mutant spinal cord (cell types expressing only TrkB.T1) the findings that TrkB.T1 deletion does not change the SOD1 spinal cord inflammatory state suggests that this receptor does not influence microglia or astrocyte activation (Zhang and Huang, 2006;Yanpallewar et al, 2012Yanpallewar et al, , 2021Just-Borras et al, 2019). These observations strongly suggest a role for TrkB.T1 in the pathophysiology of ALS and alternative ways to activate TrkB.FL may be needed to overcome the insufficient or defective TrkB signaling.…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions

Tessarollo

Yanpallewar

2022

Front. Neurosci.

Self Cite

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

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions

Tessarollo

Yanpallewar

2022

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, it was shown that the deletion of BDNF receptor TrkB.T1 delays muscle weakness and spinal cord motoneuron cell death via an unknown cellular mechanism [ 122 ]. However, the deletion of TrkB.T1 did not affect the inflammatory state of the SOD1 mutant spinal cord, implying that TrkB.T1 has no effect on the activation of astrocytes or microglia [ 123 ]. Although TrkB.T1 knockout in astrocytes retains coordination and muscle strength at the early stages of the disease, the conditional deletion of TrkB.T1 in motoneurons or astrocytes does not prevent motoneuron cell death [ 123 ].…”

Section: Bdnf In Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

“…However, the deletion of TrkB.T1 did not affect the inflammatory state of the SOD1 mutant spinal cord, implying that TrkB.T1 has no effect on the activation of astrocytes or microglia [ 123 ]. Although TrkB.T1 knockout in astrocytes retains coordination and muscle strength at the early stages of the disease, the conditional deletion of TrkB.T1 in motoneurons or astrocytes does not prevent motoneuron cell death [ 123 ]. These findings imply that TrkB.T1 may be involved in ALS pathogenesis by negatively regulating the BDNF/TrkB in motor neurons.…”

Section: Bdnf In Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

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

Azman

Zakaria

2022

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…An aberrant activation of this pathway has been described in the experimental autoimmune encephalomyelitis rodent model for multiple sclerosis, where overexpressed TrkB-T1 induces neuronal death by promoting the release of nitric oxide (Colombo et al, 2012). Moreover, astrocytic TrkB-T1 contributes to neuropathic pain and neurological dysfunctions in rodent models of spinal cord injury and of amyotrophic lateral sclerosis (Matyas et al, 2017;Yanpallewar et al, 2021). TrkB-T1 is, arguably, the predominant receptor isoform expressed in astrocytes; however, some reports have indicated that cultured astrocytes can also express full-length TrkB (Climent et al, 2000;Condorelli et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

Jaudon

Albini

Ferroni

et al. 2021

Journal of Cell Science

View full text Add to dashboard Cite

Astroglial cells are key to maintain nervous system homeostasis. Neurotrophins are known for their pleiotropic effects on neuronal physiology, but also exert complex functions onto glial cells. In this work, we investigated: (i) the signaling competence of embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF); and (ii) the role of Kinase D interacting substrate (Kidins220), a transmembrane scaffold protein that mediates neurotrophin signaling in neurons, in the astrocyte response to BDNF. We found a shift from a kinase-based response in embryonic cells to a predominantly [Ca2+]i-based response in postnatal cultures associated with the decreased expression of the full-length BDNF receptor TrkB, with a contribution of Kidins220 to the BDNF-activated kinase and [Ca2+]i pathways. Finally, Kidins220 participates in astrocytes’ homeostatic function by controlling the expression of the inwardly rectifying potassium channel (Kir) 4.1 and the metabolic balance of embryonic astrocytes. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system and identify Kidins220 as a novel actor in the increasing number of pathologies characterized by astrocytic dysfunctions.

show abstract

Delayed onset of inherited ALS by deletion of the BDNF receptor TrkB.T1 is non-cell autonomous

Cited by 18 publications

References 60 publications

TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions

TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions

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

A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

Contact Info

Product

Resources

About