Category Biology/Biotechnology

Degenerating Neurons respond to Gene Therapy for Alzheimer’s disease

Alzheimer Disease Pathology and Site of Gene Delivery in a Patient 7 Years After Gene Transfer

Alzheimer Disease Pathology and Site of Gene Delivery in a Patient 7 Years After Gene Transfer Credit: http://archneur.jamanetwork.com/article.aspx?articleid=2427383

The affected neurons displayed heightened growth, axonal sprouting and activation of functional markers after nerve growth factor (NGF) was injected into their brains.The findings are derived from postmortem analyses of 10 patients who participated in phase I clinical trials launched in 2001 to assess whether injected NGF – a protein essential to cellular growth, maintenance and survival – might safely slow or prevent neuronal degeneration in patients with AD.

Cholinergic Neuronal Hypertrophy and Sprouting

Cholinergic Neuronal Hypertrophy and Sprouting Credit: http://archneur.jamanetwork.com/article.aspx?articleid=2427383

Administering NGF directly into the brain – a fir...

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DNA Nanoscale Vehicle 1st time used to deliver CRISPR-Cas9 Gene-Editing tool into cells in both cell culture, animal model

When the nanoclew comes into contact with a cell, the cell absorbs the nanoclew completely -- swallowing it and wrapping it in a protective sheath called an endosome. But the nanoclews are coated with a positively charged polymer that breaks down the endosome, setting the nanoclew free inside the cell. The CRISPR-Cas9 complexes can then free themselves from the nanoclew to make their way to the nucleus. Credit: North Carolina State University

When the nanoclew comes into contact with a cell, the cell absorbs the nanoclew completely — swallowing it and wrapping it in a protective sheath called an endosome. But the nanoclews are coated with a positively charged polymer that breaks down the endosome, setting the nanoclew free inside the cell. The CRISPR-Cas9 complexes can then free themselves from the nanoclew to make their way to the nucleus. Credit: North Carolina State University

CRISPR-Cas system, found in bacteria and archaea, protects bacteria from invaders such as viruses. CRISPR RNA has been used in gene-editing to ID a targeted portion of relevant DNA, and Cas protein cleaves it. But for Cas9 to do its work, it must first find its way into the cell...

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Alzheimer’s disease thought to be Accelerated by an Abnormal Build-up of Fatty Acids in the Brain

Early NSC impairment in 3xTg-AD mice correlates with SVZ niche lipid accumulations • Similar lipid accumulations are found in the SVZ in postmortem human AD brains • Accumulating SVZ lipids are locally generated, oleic acid-enriched triglycerides • Inhibiting oleic acid signaling or synthesis rescues NSC defects in 3xTg-AD mice

Highlights •Early neural stem cell NSC impairment in 3xTg-AD mice correlates with SVZ subventricular zone niche lipid accumulations •Similar lipid accumulations are found in the SVZ in postmortem human AD brains •Accumulating SVZ lipids are locally generated, oleic acid-enriched triglycerides •Inhibiting oleic acid signaling or synthesis rescues NSC defects in 3xTg-AD mice Credit: Fernandes et al. Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer’s Disease. Cell Stem Cell, 27 August 2015 DOI: 10.1016/j.stem.2015.08.001

For the 1st time since the disease was described 109 years ago, researchers have discovered accumulations of fat droplets/ lipids in the brain of patients who died from the disease and h...

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Cellular Functions underlying Inflammation, Chronic disease found

Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism

Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism •Tollip TBD is a disordered domain that partially folds when bound to Tom1 GAT •Tom1 GAT also directly binds to the Tollip C2 domain •Binding of Tom1 to Tollip inhibits binding of Tollip to PtdIns(3)P •Tollip TBD plays a major role in Tom1’s inhibitory function

It has important implications for Rx of allergies, heart disease, cancer types. The discovery explains how 2 particular proteins, Tollip and Tom1, work together to contribute to the turnover of cell-surface receptor proteins that trigger inflammation...

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