Tags

Type your tag names separated by a space and hit enter

New therapeutic targets in the neurovascular pathway in Alzheimer's disease.
Neurotherapeutics. 2008 Jul; 5(3):409-14.N

Abstract

Recent findings indicate that neurovascular dysfunction is an integral part of Alzheimer's disease (AD). Changes in the vascular system of the brain may significantly contribute to the onset and progression of dementia and to the development of a chronic neurodegenerative process. In contrast to the neurocentric view, which proposes that changes in chronic neurodegenerative disorders, including AD, can be attributed solely to neuronal disorder and neuronal dysfunction, the neurovascular concept proposes that dysfunction of non-neuronal neighboring cells and disintegration of neurovascular unit function may contribute to the pathogenesis of dementias in the elderly population, and understanding these processes will be crucial for the development of new therapeutic approaches to normalize both vascular and neuronal dysfunction. In this review, I discuss briefly the role of vascular factors and vascular disorder in AD, the link between cerebrovascular disorder and AD, the clearance hypothesis for AD, the role of RAGE (receptor for advanced glycation end products) and LRP (low density lipoprotein receptor related protein 1) in maintaining the levels of amyloid beta-peptide (Abeta) in the brain by controlling its transport across the blood-brain barrier (BBB), and the role of impaired vascular remodeling and cerebral blood flow dysregulation in the disease process. The therapeutic strategies based on new targets in the AD neurovascular pathway, such as RAGE and LRP receptors, and on a few selected genes implicated in AD neurovascular dysfunction (e.g., mesenchyme homeobox gene 2 and myocardin) are also discussed.

Authors+Show Affiliations

Center for Neurodegenerative and Vascular Brain Disorders, Departments of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA. Berislav_Zlokovic@urmc.rochester.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

18625452

Citation

Zlokovic, Berislav V.. "New Therapeutic Targets in the Neurovascular Pathway in Alzheimer's Disease." Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics, vol. 5, no. 3, 2008, pp. 409-14.
Zlokovic BV. New therapeutic targets in the neurovascular pathway in Alzheimer's disease. Neurotherapeutics. 2008;5(3):409-14.
Zlokovic, B. V. (2008). New therapeutic targets in the neurovascular pathway in Alzheimer's disease. Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics, 5(3), 409-14. https://doi.org/10.1016/j.nurt.2008.05.011
Zlokovic BV. New Therapeutic Targets in the Neurovascular Pathway in Alzheimer's Disease. Neurotherapeutics. 2008;5(3):409-14. PubMed PMID: 18625452.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New therapeutic targets in the neurovascular pathway in Alzheimer's disease. A1 - Zlokovic,Berislav V, PY - 2008/7/16/pubmed PY - 2008/11/6/medline PY - 2008/7/16/entrez SP - 409 EP - 14 JF - Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics JO - Neurotherapeutics VL - 5 IS - 3 N2 - Recent findings indicate that neurovascular dysfunction is an integral part of Alzheimer's disease (AD). Changes in the vascular system of the brain may significantly contribute to the onset and progression of dementia and to the development of a chronic neurodegenerative process. In contrast to the neurocentric view, which proposes that changes in chronic neurodegenerative disorders, including AD, can be attributed solely to neuronal disorder and neuronal dysfunction, the neurovascular concept proposes that dysfunction of non-neuronal neighboring cells and disintegration of neurovascular unit function may contribute to the pathogenesis of dementias in the elderly population, and understanding these processes will be crucial for the development of new therapeutic approaches to normalize both vascular and neuronal dysfunction. In this review, I discuss briefly the role of vascular factors and vascular disorder in AD, the link between cerebrovascular disorder and AD, the clearance hypothesis for AD, the role of RAGE (receptor for advanced glycation end products) and LRP (low density lipoprotein receptor related protein 1) in maintaining the levels of amyloid beta-peptide (Abeta) in the brain by controlling its transport across the blood-brain barrier (BBB), and the role of impaired vascular remodeling and cerebral blood flow dysregulation in the disease process. The therapeutic strategies based on new targets in the AD neurovascular pathway, such as RAGE and LRP receptors, and on a few selected genes implicated in AD neurovascular dysfunction (e.g., mesenchyme homeobox gene 2 and myocardin) are also discussed. SN - 1933-7213 UR - https://www.unboundmedicine.com/medline/citation/18625452/New_therapeutic_targets_in_the_neurovascular_pathway_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1933-7213(08)00095-0 DB - PRIME DP - Unbound Medicine ER -