The contribution of ß-amyloid, Tau and α-synuclein to blood-brain barrier damage in neurodegenerative disorders.
Acta Neuropathol
; 147(1): 39, 2024 02 12.
Article
en En
| MEDLINE
| ID: mdl-38347288
ABSTRACT
Central nervous system (CNS) accumulation of fibrillary deposits made of Amyloid ß (Aß), hyperphosphorylated Tau or α-synuclein (α-syn), present either alone or in the form of mixed pathology, characterizes the most common neurodegenerative diseases (NDDs) as well as the aging brain. Compelling evidence supports that acute neurological disorders, such as traumatic brain injury (TBI) and stroke, are also accompanied by increased deposition of toxic Aß, Tau and α-syn species. While the contribution of these pathological proteins to neurodegeneration has been experimentally ascertained, the cellular and molecular mechanisms driving Aß, Tau and α-syn-related brain damage remain to be fully clarified. In the last few years, studies have shown that Aß, Tau and α-syn may contribute to neurodegeneration also by inducing and/or promoting blood-brain barrier (BBB) disruption. These pathological proteins can affect BBB integrity either directly by affecting key BBB components such as pericytes and endothelial cells (ECs) or indirectly, by promoting brain macrophages activation and dysfunction. Here, we summarize and critically discuss key findings showing how Aß, Tau and α-syn can contribute to BBB damage in most common NDDs, TBI and stroke. We also highlight the need for a deeper characterization of the role of these pathological proteins in the activation and dysfunction of brain macrophages, pericytes and ECs to improve diagnosis and treatment of acute and chronic neurological disorders.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Neurodegenerativas
/
Accidente Cerebrovascular
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
Acta Neuropathol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Finlandia