title: The blood-brain barrier in Alzheimer's disease: novel therapeutic targets and nanodrug delivery.
abstract: Treatment strategies for Alzheimer's disease (AD) are still elusive. Thus, new strategies are needed to understand the pathogenesis of AD in order to provide suitable therapeutic measures. Available evidences suggest that in AD, passage across the blood-brain barrier (BBB) and transport exchanges for amyloid-β-peptide (ABP) between blood and the central nervous system (CNS) compartments play an important regulatory role for the deposition of brain ABP. New evidences suggest that BBB is altered in AD. Studies favoring transport theory clearly show that ABP putative receptors at the BBB control the level of soluble isoform of ABP in brain. This is achieved by regulating influx of circulating ABP into brain via specific receptor for advanced glycation end products (RAGE) and gp330/megalin-mediated transcytosis. On the other hand, the efflux of brain-derived ABP into the circulation across the vascular system via BBB is accomplished by low-density receptor-related protein-1 (LRP1). Furthermore, an increased BBB permeability in AD is also likely since structural damage of endothelial cells is quite frequent in AD brain. Thus, enhanced drug delivery in AD is needed to induce neuroprotection and therapeutic success. For this purpose, nanodrug delivery could be one of the available options that require active consideration for novel therapeutic strategies to treat AD cases. This review is focused on these aspects and provides new data showing that BBB plays an important role in AD-induced neurodegeneration and neurorepair.
authors: Cerebrovascular Research Laboratory, Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, Uppsala, Sweden.
authors: Hari Shanker
authors: HS
authors: Sharma
authors: Rudy J
authors: RJ
authors: Castellani
authors: Mark A
authors: MA
authors: Smith
authors: Aruna
authors: A
authors: Sharma
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D036103:Nanotechnology / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides