Blogs for October 2017

Polyglutamine Tracts as Autophagy Regulators

Tuesday, October 31, 2017 - 09:20

By Yoskaly Lazo-Fernandez, PhD

Polyglutamine tracts (polyQ tracts) are long chains of glutamine amino acidspresent in the sequence of many proteins. The length of polyQ tracts within proteins varies significantly as normal alleles of specific genes usually contain different number of the cytosine-adenine-guanine (CAG) nucleotide repeats1.

It has long been known that polyQ tracts play a role in the etiology of several inheritable neurodegenerative disorders, including spinocerebellar ataxia, and Huntington's disease2. These 'polyglutamine diseases' result from the excessive elongation of a polyQ tract in a particular gene which causes the resultant protein to become toxic. The toxicity of mutated polyQ tracts has been extensively studied and several explanatory hypotheses have been proposed: aggregation of polyQ tract proteins, transcriptional dysregulation, mitochondrial dysfunction, and impairment of both the ubiquitin-...

Autophagy and Apoptosis: who regulates whom?

Monday, October 23, 2017 - 13:13

By Christina Towers, PhD

Apoptosis, or programmed cell death, is the result of an intricate cascade of signaling events that is initiated by extrinsic (death receptor mediated) and intrinsic (mitochondrial mediated) stimuli.  Extrinsic apoptosis is initiated by ligand binding to death receptors followed by signaling cascades that activate caspase-8, also known as the initiator caspase.  The effector caspase-3 can be activated by caspase-8, but is usually activated downstream of the intrinsic pathway, and often the extrinsic pathway will converge on the intrinsic for more efficient programmed cell death. Intrinsic signaling takes place on the mitochondrial membrane, where BH-3 only proteins activate mitochondrial outer membrane permeabilization (MOMP) and the release of mitochondrial proteins like cytochrome c.  Subsequently, the apoptosome is formed by a...

Beyond Genes: Treating Memory Loss with Minimum Adverse Effects

Tuesday, October 17, 2017 - 12:43

By Jamshed Arslan Pharm.D.

Alzheimer’s disease (AD) robs people of their memory and identity. One characteristic feature of AD is the increased expression of the enzyme, histone deacetylase-2 (HDAC-2). This protein stops the expression of some memory-forming genes by condensing them. So, memory can be enhanced by inhibiting HDAC-2. However, this approach is dangerous since HDAC-1, a close family member of HDAC-2, would also become inhibited, resulting in neuronal death and other toxic effects. New research,[1] led by Li-Huei Tsai at the Massachusetts Institute of Technology, Cambridge, suggests a novel way to specifically repress HDAC-2 by targeting the domain of HDAC-2 that makes a complex with the transcription factor, Sp3.


There's an autophagy for that!

Tuesday, October 10, 2017 - 13:09

By Christina Towers, PhD

A critical mechanism that cells use to generate nutrients and fuel metabolism is through a process called autophagy.  This process is complex and involves over 20 different proteins, most of which are highly conserved across species.  It involves the formation of a double membrane structure known as an autophagasome that fuses with the lysosome to facilitate the degradation of cytoplasmic material.  While bulk autophagy is thought to be largely non-specific, clearing damaged proteins from the cytoplasm, recent studies have begun to highlight more selective forms of autophagy.  Selective autophagy, also coined organellophagy, facilitates the degradation of specific organelles that are damaged or targeted for recycling.  Thus far, researchers have begun to investigate the selective degradation of mitochondria, peroxisomes, endoplasmic reticulum (ER), nuclei, and chloroplasts in plants, all mediated through variant forms of...

HIF-1 alpha and HIF-2 alpha in Muscle Development

Tuesday, October 3, 2017 - 11:42

By Bethany Veo, PhD

Our muscle cells develop from myogenic stem cells or satellite cells which have the capacity to grow, self-renew, differentiate, and regenerate under the influence of changing oxygen levels sensed from the microenvironment. Hypoxia-inducible factors HIF-1 alpha and HIF-2 alpha are transcription factors that respond to low oxygen levels, activating the expression of target genes. The current understanding of the role that HIF-1 alpha and HIF-2 alpha play in muscle development is contradictory. Case in point, upregulation and downregulation of HIF-1 alpha inhibit myoblast differentiation depending on the oxygen level in vitro.

Transgenic models including mice lacking HIF-2 alpha exhibit early embryonic arrest and HIF-1 alpha knockouts are lethal. Whereas HIF-1 alpha knockouts generated with a different Cre-...

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