Wednesday, May 6, 2020

A Research Study On Calcium Dependent Cytosolic Rat Brains...

Calpain was first discovered within the brain, lens of eyes and other tissues by Gordon Guroff in 1964. This was done by isolating enzymes in both rat brains and skeletal muscles. These findings concluded that Calpains are calcium-dependent cytosolic cysteine proteinases. With further research, it was noted that Calpains are found in nearly all eukaryotes as well as some types of bacteria but, not within archaebacterial domain. Structurally, Calpains contain four functional domains with two domains that serve as regulatory subunits. In general, Calpains have multiple functions such as cell cycle progression, cell differentiation, membrane fusion, signal transduction, membrane fusion, apoptosis and myogenesis (Khorchid Mitsuhiko, 2002).†¦show more content†¦Only a few classical Calpains have been identified within invertebrates. Specifically for human Calpain genes, there are nine classical Calpains and six non-classical Calpains, giving a total of 15 Calpain genes for human s. For human Calpain genes, there two genes for regulatory subunits and one specific inhibitor protein. Classical Calpains, especially those found in humans, are ubiquioltly expressed and are controlled through the inhibitor of Calpastain (Trinchese et al., 2008). Although the role of calcium inducing change to enable Calpastatin to bind to Calpain is unknown, it is seen that Calpain 2 is bounded by inhibitory domains of Calpastatin which are inhibiting Calpain from both sides of the active site cleft. From this it was assumed that Calpastatin not only recognizes that there are multiple lower affinity sites but, that they are only present in the calcium-bound form of the enzyme which results in the interaction between Calpain and Calpastatin to be tight, specific and calcium dependent (Hanna, Campbell, Davies, 2008). Aside from Calpains causing cells to migrate, differentiate, proliferate and die, activation of Calpains have been linked to the pathogenesis of Alzheimer’s Disease. 5 million individuals have been diagnosed with Alzheimer’s Disease with an increase of 68 percent from 2000-2010, making it the sixth leading cause of death within

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