1. AQUAPORINS IN NEURODEGENERATIVE DISORDERS AND SCHIZOPHRENIA
Aquaporins are membrane proteins that belong to a family called major intrinsic proteins
(MIP) that form pores in the membrane of biological cells through which water circulates
in an organized way. Aquaporins are the plumbing system of the cells and in 2003 Peter
Agre from John Hopkins University was awarded Nobel Prize in Chemistry for their
discovery. Here is an animation about aquaporins:
http://www.youtube.com/watch?v=ERTkE91ICB8
Aquaporins 4 are specific water receptors found in the brain and are supposed to play an
important role in regulating neuronal environment, but why care about them?
Apoptosis has been considered to be involved in neurodegenerative disorders and
schizophrenia. Water receptors are modulated just before apoptosis occurs. A recent
study reveals a novel role of aquaporin 4 in the uptake of A-beta amyloid by astrocytes,
identifying it as a molecular target for Alzheimer’s disease. Read more at:
http://www.sciencedirect.com/science/article/pii/S1044743112000243
Here is a study published this month demonstrating that certain polymorphisms of
aquaporin 4 receptors influence the optimal dose of antipsychotics used in schizophrenia.
The study concluded that patients with the AQP-4 non-C polymorphism needed a higher
dosage of olanzapine for treatment (z = 4.163, P = 0.041), and patients with a short form
of the MAOA polymorphism needed a higher dosage of risperidone for treatment (z =
5.124, P = 0.024).
This study can be found at: http://www.ncbi.nlm.nih.gov/pubmed/22544010
Aquaporins are also involved in neuroinflammation possibly by autoimmune
mechanisms. For instance neuromyelitis optica (NMO) is associated with highly specific
serum auto-antibodies to aquaporin-4 (termed AQP4-Ab). Recent evidence strongly
suggests that AQP4-Ab are directly involved in the immunopathogenesis of NMO and
possibly multiple sclerosis. Read more Read more at:
http://www.jneuroinflammation.com/content/7/1/52
What is even more interesting is that influenza infection in mid-pregnancy results in
decreased brain expression of aquaporin 4 receptors. This may explain why maternal
exposure to influenza constitutes an increased risk of schizophrenia in offspring:
http://www.mendeley.com/research/viral-regulation-of-aquaporin-4-connexin-43-
microcephalin-and-nucleolin/
ADONIS SFERA, MD