SARM1 Forefronts Research into Major Neurological Diseases

SARM1 Causes Axonal Death
SARM1 [Sterile alpha & toll/interleukin receptor (TIR) motif-containing protein 1] consists of a N-terminal mitochondrial localization sequence (NLS), an autoinhibitory HEAT/armadillo (ARM) domain, two tandem sterile alpha motif domains (SAMs), and a C-terminal toll/interleukin receptor domain (TIR). It is a human toll like receptor (TLR) adaptor protein. TLR adaptors (MYD88, MAL, TRIF, & TRAM) usually
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SIRT2 Isoforms in Neurodegenerative Diseases & Cancer

SIRT2 Affects Neurodegenerative Diseases
Silent information regulator type 2 (Sirtuin 2 or SIRT2) is a highly evolutionarily conserved NAD+ dependent deacetylase. SIRT2 is the only Sirtuin that acts in the cytosol. It expresses in almost all tissues, but most abundantly in the central nervous system. While SIRT2 is classified as a type III histone deacetylase, it is also capable
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Targeting Adenosine Kinase in the Fight Against Neurological Disorders

Targeting Adenosine Kinase In the Fight Against Neurological Disorders
Could targeting Adenosine Kinase help lead to treatments for neurological disorders and chronic pain? Adenosine, one of four nucleoside building blocks to DNA and RNA, has a shielding effect on a wide range of conditions, including inflammation, various forms of neuronal hyperexcitability, and/or toxicity, including hypoxia, seizures, and chronic pain. This cellular activity modulator brings
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The Curious Neuroprotective Effects of Protein Kinase A-active Agents

The impact of neurodegenerative disorders is profound. An estimated 1 million people in the U.S. endure Parkinson’s disease1, and another 5.3 million live with Alzheimer’s disease2. Over 69,000 ischemic strokes occur each year in the U.S.3, and those lucky enough to survive them are at risk for neurodegeneration. There is tremendous need for a better
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Targeting Phosphodiesterase 4B for Cognitive Disorders

Cognitive dysfunction, including loss of core functions such as memory, learning and reasoning occurs in many psychiatric disorders, and impairs the quality of life for millions of older adults suffering from dementia. As there is no single cause, treatments vary. However the few drugs that are available, most of which boost neurotransmitter levels, are not
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RGS4 Inhibitor Shows Activity in Parkinson’s Disease Model

RGS (regulator of G-protein signaling) proteins attenuate GPCR signals and provide an intriguing alternative to direct receptor targeting for modulating GPCR pathways. A recent effort led by Richard Neubig at Michigan State University (Blazer, et al ACS Chem Neurosci. 2015 Apr 20) provides a big boost to validation of RGS proteins as drug targets. Their
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Brain Penetrant LRRK2 GTPase Inhibitor Shows Promise For PD

Parkinson’s disease (PD), a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons, currently affects nearly 7 million people worldwide.  Mutations in leucine-rich repeat kinase 2 (LRRK2), a dual functional protein with separate kinase and GTPase domains, are the most common cause of autosomal dominant PD and also contribute to sporadic PD. Multiple lines
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Pharmacoperones: Correcting Misfolded Proteins, Curing Disease.

Researchers from Oregon Health and Science University (OHSU), led by P. Michael Conn, have demonstrated in mice a novel technique used to cure disease caused by misfolded protein molecules.  The same technique could be used to cure human diseases with similar etiology.    Human diseases caused by misfolded proteins are diverse and numerous.  Among them
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The Smell Test: Peanut Butter and Alzheimer’s

New research suggests peanut butter as innovative diagnostic tool.  Imagine: you wake up one day to find you can no longer enjoy the scent of peanut butter.  Now imagine this: you wake up two years later to find you can no longer remember your spouse’s name.  Could the first unfortunate scenario be a pre-cursor to
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