Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis?
A growing wave of evidence has placed the concept of protein homeostasis at the center of the pathogenesis of amyotrophic lateral sclerosis (ALS). This is due primarily to the presence of pathological transactive response DNA-binding protein (TDP-43), fused in sarcoma (FUS) or superoxide dismutase-1...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.997661/full |
| _version_ | 1811209791612125184 |
|---|---|
| author | Jeremy S. Lum Jeremy S. Lum Justin J. Yerbury Justin J. Yerbury |
| author_facet | Jeremy S. Lum Jeremy S. Lum Justin J. Yerbury Justin J. Yerbury |
| author_sort | Jeremy S. Lum |
| collection | DOAJ |
| description | A growing wave of evidence has placed the concept of protein homeostasis at the center of the pathogenesis of amyotrophic lateral sclerosis (ALS). This is due primarily to the presence of pathological transactive response DNA-binding protein (TDP-43), fused in sarcoma (FUS) or superoxide dismutase-1 (SOD1) inclusions within motor neurons of ALS postmortem tissue. However, the earliest pathological alterations associated with ALS occur to the structure and function of the synapse, prior to motor neuron loss. Recent evidence demonstrates the pathological accumulation of ALS-associated proteins (TDP-43, FUS, C9orf72-associated di-peptide repeats and SOD1) within the axo-synaptic compartment of motor neurons. In this review, we discuss this recent evidence and how axo-synaptic proteome dyshomeostasis may contribute to synaptic dysfunction in ALS. |
| first_indexed | 2024-04-12T04:44:52Z |
| format | Article |
| id | doaj.art-9c316299a17e43e2a1fbe931e6abb243 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-12T04:44:52Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-9c316299a17e43e2a1fbe931e6abb2432022-12-22T03:47:32ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-09-011510.3389/fnmol.2022.997661997661Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis?Jeremy S. Lum0Jeremy S. Lum1Justin J. Yerbury2Justin J. Yerbury3Illawarra Health and Medical Research Institute, Wollongong, NSW, AustraliaMolecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, AustraliaIllawarra Health and Medical Research Institute, Wollongong, NSW, AustraliaMolecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, AustraliaA growing wave of evidence has placed the concept of protein homeostasis at the center of the pathogenesis of amyotrophic lateral sclerosis (ALS). This is due primarily to the presence of pathological transactive response DNA-binding protein (TDP-43), fused in sarcoma (FUS) or superoxide dismutase-1 (SOD1) inclusions within motor neurons of ALS postmortem tissue. However, the earliest pathological alterations associated with ALS occur to the structure and function of the synapse, prior to motor neuron loss. Recent evidence demonstrates the pathological accumulation of ALS-associated proteins (TDP-43, FUS, C9orf72-associated di-peptide repeats and SOD1) within the axo-synaptic compartment of motor neurons. In this review, we discuss this recent evidence and how axo-synaptic proteome dyshomeostasis may contribute to synaptic dysfunction in ALS.https://www.frontiersin.org/articles/10.3389/fnmol.2022.997661/fullproteostasisaxo-synaptic compartmentprotein misfoldingsynapseamyotrophic lateral sclerosis |
| spellingShingle | Jeremy S. Lum Jeremy S. Lum Justin J. Yerbury Justin J. Yerbury Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis? Frontiers in Molecular Neuroscience proteostasis axo-synaptic compartment protein misfolding synapse amyotrophic lateral sclerosis |
| title | Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis? |
| title_full | Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis? |
| title_fullStr | Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis? |
| title_full_unstemmed | Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis? |
| title_short | Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis? |
| title_sort | misfolding at the synapse a role in amyotrophic lateral sclerosis pathogenesis |
| topic | proteostasis axo-synaptic compartment protein misfolding synapse amyotrophic lateral sclerosis |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.997661/full |
| work_keys_str_mv | AT jeremyslum misfoldingatthesynapsearoleinamyotrophiclateralsclerosispathogenesis AT jeremyslum misfoldingatthesynapsearoleinamyotrophiclateralsclerosispathogenesis AT justinjyerbury misfoldingatthesynapsearoleinamyotrophiclateralsclerosispathogenesis AT justinjyerbury misfoldingatthesynapsearoleinamyotrophiclateralsclerosispathogenesis |