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.
| Original language | English (US) |
|---|---|
| Title of host publication | International Review of Neurobiology |
| Publisher | Academic Press Inc |
| Pages | 47-90 |
| Number of pages | 44 |
| DOIs | |
| State | Published - 2012 |
Publication series
| Name | International Review of Neurobiology |
|---|---|
| Volume | 102 |
| ISSN (Print) | 0074-7742 |
Funding
The research reported in this review is supported by grants from the Alzheimer's Association (IIRG-09-132087), the National Institutes of Health (R01 AG028679), the Dr. Robert M. Kohrman Memorial Fund (M.A.S., R.J.C.), and Swedish Medical Research Council (nr 2710 H.S.S.). Investigations on nanotechnology in AD and nanowired drug delivery reported in this review are supported in part by European Office of Aerospace Research & Development (EOARD) London Office, London, UK and Wright Patterson Air Force Research Laboratory (WPAFB), Dayton, OH, USA (HSS/AS), and Laerdal Foundation of Acute Medicine, Stavanger, Norway (HSS). Secretarial assistance of Gunilla Åberg and Technical assistance of Kerstin Flink, Ingmarie Olsson, and Mari-Anne Carlsson (Uppsala) is highly appreciated. The authors (HSS/AS) are grateful to Berislav Zlokovic for critically reading an earlier version of the draft manuscript dealing with his works on AD and allowing some of his data to be included in this review. We deeply appreciate our fruitful discussion with Raj Kalaria on various aspects of cerebrovascular involvement in AD described in this work. We thank the reviewers for their valuable suggestions and comments to improve the chapter with regard to inclusion of new drug targets in AD.
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience