First drawing in a review !!
http://link.springer.com/article/10.1007%2Fs12035-013-8435-5
Peroxisome Proliferator-activated Receptors and Alzheimer's Disease: Hitting the Blood–Brain Barrier
Juan M. Zolezzi and Nibaldo C. Inestrosa
The blood–brain barrier (BBB) is often affected in several
neurodegenerative disorders, such as Alzheimer's disease (AD). Integrity
and proper functionality of the neurovascular unit are recognized to be
critical for maintenance of the BBB. Research has traditionally focused
on structural integrity more than functionality, and BBB alteration has
usually been explained more as a consequence than a cause. However,
ongoing evidence suggests that at the early stages, the BBB of a
diseased brain often shows distinct expression patterns of specific
carriers such as members of the ATP-binding cassette (ABC) transport
protein family, which alter BBB traffic. In AD, amyloid-β (Aβ) deposits
are a pathological hallmark and, as recently highlighted by Cramer et
al. (2012), Aβ clearance is quite fundamental and is a less studied
approach. Current knowledge suggests that BBB traffic plays a more
important role than previously believed and that pharmacological
modulation of the BBB may offer new therapeutic alternatives for AD.
Recent investigations carried out in our laboratory indicate that
peroxisome proliferator-activated receptor (PPAR) agonists are able to
prevent Aβ-induced neurotoxicity in hippocampal neurons and cognitive
impairment in a double transgenic mouse model of AD. However, even when
enough literature about PPAR agonists and neurodegenerative disorders is
available, the problem of how they exert their functions and help to
prevent and rescue Aβ-induced neurotoxicity is poorly understood. In
this review, along with highlighting the main features of the BBB and
its role in AD, we will discuss information regarding the modulation of
BBB components, including the possible role of PPAR agonists as BBB
traffic modulators.
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