Targeting lysyl-oxidase (LOX) may facilitate intramural periarterial drainage for the treatment of Alzheimer's disease
Kelly, Louise (University of Southampton)
Sharp, Matthew Macgregor (University of Southampton)
Thomas, Isabelle (Cardiff University)
Brown, Christopher (University of Southampton)
Schrag, Matthew (Vanderbilt Brain Institute. Vanderbilt University)
Antunes, Lissa Ventura (Vanderbilt Brain Institute. Vanderbilt University)
Solopova, Elena (Vanderbilt Brain Institute. Vanderbilt University)
Martínez-González, José Pablo (Institut d'Investigació Biomèdica Sant Pau)
Rodríguez, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Carare, Roxana Octavia (University of Southampton)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	Alzheimer's disease is the commonest form of dementia. It is likely that a lack of clearance of amyloid beta (Aβ) results in its accumulation in the parenchyma as Aβ oligomers and insoluble plaques, and within the walls of blood vessels as cerebral amyloid angiopathy (CAA). The drainage of Aβ along the basement membranes of blood vessels as intramural periarterial drainage (IPAD), could be improved if the driving force behind IPAD could be augmented, therefore reducing Aβ accumulation. There are alterations in the composition of the vascular basement membrane in Alzheimer's disease. Lysyl oxidase (LOX) is an enzyme involved in the remodelling of the extracellular matrix and its expression and function is altered in various disease states. The expression of LOX is increased in Alzheimer's disease, but it is unclear whether this is a contributory factor in the impairment of IPAD in Alzheimer's disease. The pharmacological inhibition of LOX may be a strategy to improve IPAD and reduce the accumulation of Aβ in the parenchyma and within the walls of blood vessels.
Ajuts:	Instituto de Salud Carlos III PI21/01048 Agencia Estatal de Investigación PID2021-122509OB-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Amyloid beta ; Basement membrane ; Cerebral amyloid angiopathy ; Dementia ; Lysyl oxidase
Publicat a:	Cerebral Circulation - Cognition and Behavior, Vol. 5 (january 2023) , p. 100171, ISSN 2666-2450

DOI: 10.1016/j.cccb.2023.100171
PMID: 37457664

8 p, 5.8 MB

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