Mitogen-activated protein kinases and the evolution of Alzheimer's: a revolutionary neurogenetic axis for therapeutic intervention?
Alzheimer's disease (AD) is a neurogenetic condition that affects the processes via which the brain functions. Major observable hallmarks of AD are accumulated clusters of proteins in the brain. These clusters, termed neurofibrillary tangles (NFT), resemble pairs of threads wound around each other in a helix fashion accumulating within neurons. These tangles consist of a protein called Tau, which binds to tubulin, thus forming microtubules. Unlike NFTs, deposits of amyloid precursor protein (beta-APP) gather in the spaces between nerve cells. The nearby neurons often look swollen and deformed, and the clusters of protein are usually accompanied by reactive inflammatory cells, microglia, which are part of the brain's immune system responsible for degrading and removing damaged neurons or plaques. Since phosphorylation/dephosphorylation mechanisms are crucial in the regulation of Tau and beta-APP, a superfamily of mitogen-activated protein kinases (MAPKs) has recently emerged as key regulators of the formation of plagues, eventually leading to dementia and AD. The complex molecular interactions between MAPKs and proteins (plagues) associated with the evolution of AD form a cornerstone in the knowledge of a still burgeoning field of neurodegenerative diseases and ageing. This review overviews current understanding of the molecular pathways related to MAPKs and their role in the development of AD and, possibly, dementia. MAPKs, therefore, may constitute a neurogenetic, therapeutic target for the diagnosis and evolution of a preventative medical strategy for early detection, and likely treatment, of Alzheimer's.
Severinghaus-Radiometer Research Laboratories, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA. johnjhaddad@yahoo.co.uk
John J
JJ
Haddad
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D004791:Enzyme Inhibitors; D020928:Mitogen-Activated Protein Kinases