Wallerian degeneration as a therapeutic target in traumatic brain injury.
Curr Opin Neurol
; 32(6): 786-795, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31633494
ABSTRACT
PURPOSE OF REVIEW Diffuse or traumatic axonal injury is one of the principal pathologies encountered in traumatic brain injury (TBI) and the resulting axonal loss, disconnection, and brain atrophy contribute significantly to clinical morbidity and disability. The seminal discovery of the slow Wallerian degeneration mice (Wld) in which transected axons do not degenerate but survive and function independently for weeks has transformed concepts on axonal biology and raised hopes that axonopathies may be amenable to specific therapeutic interventions. Here we review mechanisms of axonal degeneration and also describe how these mechanisms may inform biological therapies of traumatic axonopathy in the context of TBI. RECENT FINDINGS:
In the last decade, SARM1 [sterile a and Toll/interleukin-1 receptor (TIR) motif containing 1] and the DLK (dual leucine zipper bearing kinase) and LZK (leucine zipper kinase) MAPK (mitogen-activated protein kinases) cascade have been established as the key drivers of Wallerian degeneration, a complex program of axonal self-destruction which is activated by a wide range of injurious insults, including insults that may otherwise leave axons structurally robust and potentially salvageable. Detailed studies on animal models and postmortem human brains indicate that this type of partial disruption is the main initial pathology in traumatic axonopathy. At the same time, the molecular dissection of Wallerian degeneration has revealed that the decision that commits axons to degeneration is temporally separated from the time of injury, a window that allows potentially effective pharmacological interventions.SUMMARY:
Molecular signals initiating and triggering Wallerian degeneration appear to be playing an important role in traumatic axonopathy and recent advances in understanding their nature and significance is opening up new therapeutic opportunities for TBI.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Degeneração Walleriana
/
Lesões Encefálicas Difusas
/
Lesões Encefálicas Traumáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Opin Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article