Blogs for September 2017

Necroptosis in Health and Disease

Tuesday, September 26, 2017 - 09:22

By Bethany Veo, PhD

Necroptosis occurs when cells fail to undergo apoptosis following inflammatory, oxidative or ischemic stressors. Necroptotic cell death removes damaged cells and cells no longer critical for development, independently of caspase activation.  Whereas apoptotic cells display condensed nuclei and fragmentation, the telltale signs of necroptosis are plasma membrane permeabilization and mitochondria swelling.  As a regulated cell death mechanism, the process of necroptosis is necessary for maintaining cellular homeostasis during development and as a response to cellular stress conditions.  

Initiation of necroptosis results from blocking pro-survival cues from inhibitors of apoptosis.  Signaling through TNFa (tumor necrosis factor), FASL (FAS ligand) and TRAIL (Tumor...

PINK1 as a Mitochondrial Health Sensor and Neuroprotector

Tuesday, September 19, 2017 - 09:40

By Bethany Veo, PhD

Mitochondria are most commonly known as the power houses of the cell, facilitating major functions such as oxidative phosphorylation and cellular respiration.  Maintenance of mitochondria is essential to a cells' physiological homeostasis and requires oversight by several factors.  PINK1 is a serine/threonine protein kinase which localizes to the mitochondrion and regulates its function and turnover by sensing when mitochondria are damaged.1  The foremost mechanisms of mitochondrial health upkeep include fusion and fission, mitophagy, and mitochondrial transport. PINK1 is critical for mitochondrial health by facilitating all of these pathways, which serve as a quality control system to remove dysfunctional or damaged mitochondrion from the cell.  In fact, mutations in PINK1 are linked with Parkinson's disease, where dysfunction in mitophagy, mitochondrial clearance and...

Autophagy: Pro or Anti-tumorigenic? And the role of epigenetics in this debate

Monday, September 11, 2017 - 11:26

By Christina Towers, PhD

Autophagy is an evolutionarily conserved process that cells use to break down damaged cytoplasmic constituents in order to fuel cellular metabolism, particularly in instances of stress. This process has been heavily implicated in a variety of diseases, most noteworthy are neurological disorders and cancer. The role of autophagy in cancer is context dependent and somewhat controversial1. It was originally suggested by Dr. Beth Levine's group that autophagy is tumor suppressive, a claim supported by loss of the core autophagy gene, BECN1, in many tumor types including breast, prostrate, and ovarian2. However, critics of this notion point out the important observation that BECN1 is adjacent to the heavily deleted tumor suppressor gene, BRCA1,...

The Proteasome and Autophagy Pathways in Alzheimer's Disease

Tuesday, September 5, 2017 - 09:42

The neurodegenerative disorder, Alzheimer's disease, is responsible for 60 to 80% of all dementia cases.1   Neurodegeneration occurs in response to the accumulation of amyloid-β plaques and neurofibrillary tangles composed of hyperphosphorylated tau. The proteolytic processing of AβPP (amyloid β precursor protein) by β-secretase and γ-secretase releases Aβ fragments of 40 and 42 amino acid residues which miss-fold and aggregate into the pathogenic plaques.2  Similarly, proteolytic processing of phosphorylated tau releases monomers that are targeted to the 26S proteasome for degradation. However, proteasomal efficiency is poor when it comes to degrading ubiquitinated tau as these substrates lead to more neurofibrillary tangle aggregates.2 The inability to clear these accumulating plaques intracellularly results in a significant amount of oxidative and cellular stress leading to progressive neuronal loss and...

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