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Advances in Gene Delivery Methods to Label and Modulate Activity of Upper Motor Neurons: Implications for Amyotrophic Lateral Sclerosis

Brain sciences, 2021-08, Vol.11 (9), p.1112 [Peer Reviewed Journal]

2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2021 by the authors. 2021 ;ISSN: 2076-3425 ;EISSN: 2076-3425 ;DOI: 10.3390/brainsci11091112 ;PMID: 34573134

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  • Title:
    Advances in Gene Delivery Methods to Label and Modulate Activity of Upper Motor Neurons: Implications for Amyotrophic Lateral Sclerosis
  • Author: Haidar, Mouna ; Viden, Aida ; Turner, Bradley J.
  • Subjects: Amyotrophic lateral sclerosis ; Animal models ; Brain architecture ; Brain stem ; Cortex (motor) ; Cytomegalovirus ; Degeneration ; Gene expression ; Gene mapping ; Gene transfer ; Genetic engineering ; Kinases ; Labeling ; motor cortex ; Motor neurons ; Neurons ; Physiology ; Population studies ; Proteins ; reporter mouse models ; retrograde tracing ; Review ; Spinal cord ; Therapeutic targets ; Transgenic mice ; upper motor neurons ; Vectors (Biology) ; viral vectors
  • Is Part Of: Brain sciences, 2021-08, Vol.11 (9), p.1112
  • Description: The selective degeneration of both upper motor neurons (UMNs) and lower motor neurons (LMNs) is the pathological hallmark of amyotrophic lateral sclerosis (ALS). Unlike the simple organisation of LMNs in the brainstem and spinal cord, UMNs are embedded in the complex cytoarchitecture of the primary motor cortex, which complicates their identification. UMNs therefore remain a challenging neuronal population to study in ALS research, particularly in the early pre-symptomatic stages of animal models. A better understanding of the mechanisms that lead to selective UMN degeneration requires unequivocal visualization and cellular identification of vulnerable UMNs within the heterogeneous cortical neuronal population and circuitry. Here, we review recent novel gene delivery methods developed to cellularly identify vulnerable UMNs and modulate their activity in various mouse models. A critical overview of retrograde tracers, viral vectors encoding reporter genes and transgenic reporter mice used to visualize UMNs in mouse models of ALS is provided. Functional targeting of UMNs in vivo with the advent of optogenetic and chemogenetic technology is also discussed. These exciting gene delivery techniques will facilitate improved anatomical mapping, cell-specific gene expression profiling and targeted manipulation of UMN activity in mice. These advancements in the field pave the way for future work to uncover the precise role of UMNs in ALS and improve future therapeutic targeting of UMNs.
  • Publisher: Basel: MDPI AG
  • Language: English
  • Identifier: ISSN: 2076-3425
    EISSN: 2076-3425
    DOI: 10.3390/brainsci11091112
    PMID: 34573134
  • Source: PubMed Central
    ROAD: Directory of Open Access Scholarly Resources
    ProQuest Central
    DOAJ Directory of Open Access Journals
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