January 13, 2014

Nat med 2004 jul10 suppls10 7 review nf neurofilament

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Unformatted text preview: HD, ubidiquitin and huntingtin found in the brain However, the cell cannot always remove aggregates ALS, contain ubidquitin and SOD1 • In ALS • Insoluble cytoplasmic inclusions are composed of SOD1 protein and ubiquitin Ross CA, Poirier MA. Nat Med. 2004 Jul;10 Suppl:S10-7. Review. NF- neurofilament Aggregates: Cause or consequence? • Most neurodegenerative diseases are characterized by intracellular or extracellular deposition of inslouble material • Whether this is a cause or consequence of the disease remains unknown • Speculated that the early species in this process might be most toxic – interacting abnormally with other cellular proteins Common Features - Mitochondrial dysfunction and oxidative stress • The role of the mitochondria is to produce ATP (energy for the cell) through a process called oxidative phosphorylation • This process produces reactive oxygen species (ROS) which are harmful to the cell • To protect against ROS damage, mitochondria contain a variety of antioxidant mechanisms the most 2 common ( Mitochondrial dysfunction -ATP energy for cell -reactive species, byproducts are harmful to the cell/ cell have protected way against oxidative reactive specie Oxidative Phosphorylation • Process occurs due to a complex system of redox reactions that moves H+ and e- between the inner membrane and outer space of the mitochondrion, generating a gradient that moves the reactions Makes lots of energy/ gives detrimental effect to the cell/ we have enzymes against the free radicals / they get rid of / break down / neutralize the redox reaction Mitochondria Dysfunction Toxic mitochondria - as it gets damaged/ smaller/ shortened/very small/ eventually get sensitized / how Oxidative stress toxic/ oxidation of proteins / all get oxidized/ when this happens/ we lose function- cell death Damaged Hypoxic Normal www.alsa.org Pharmaceuticals 2010, 3(1), 158-187 How is oxidative stress toxic? • Promotes the oxidation of • Proteins • Lipids • Catecholamines (epinephrine, dopamine) • DNA • Loss of function, impaired...
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