Drug cuts tau tangles to fight dementia in mice

Drug cuts tau tangles to fight dementia in mice

Publication date: Apr 09, 2019

However, when soluble, stable tau misfolds-sometimes the result of a mutation of the gene that expresses it-the resulting protein becomes insoluble and tangled, gumming up the works inside the neuron as a neurofibrillary tangle.

-People had already talked about this gene as possibly involved in Huntington’s disease, which is another neurodegenerative disease,” Kosik says.

Researchers consider RASD2 and its more famous cousin RAS (studied heavily in cancer research) -druggable,” Kosik explains.

Such has been the case for Kosik and the paper’s lead author, postdoctoral researcher Israel Hernandez, who have for years studied tau tangles and the protein coding genes that could contribute to or counteract tau misfolding.

Kosik, Hernandez, and their colleagues’ combination of expertise and curiosity led them to examine a GTPase called Rhes, which the gene RASD2 encodes and research has shown to play a role in the development of Huntington’s disease.

Like its cousins in the Ras superfamily, Rhes is a signaling protein that does its work on the cell surface, where, Kosik explains, a small carbon chain-a farnesyl group-attaches it to the inner membrane through a process called farnesylation.

This attachment has been the target of a couple decades and millions of dollars of cancer research under the assumption that if researchers could interrupt the Ras protein connection to the cell membrane, that would interrupt the signals that cause unregulated growth of tumor cells and other cancer behaviors.

-The drug is very interesting,” Kosik says, -It seems to have a selective effect on only the forms of tau that are predisposed to forming the neurofibrillary tangles. “

To prove the drug was targeting the farnsylated Rhes protein, the scientists introduced into the brains of other mouse models an inhibitory RNA gene that specifically suppresses the production of Rhes.

-This makes us begin to think that although indeed the drug is a general farnesyl transferase inhibitor, one way it’s actually working is by specifically targeting the farnesylation of Rhes,” Kosik says.

And perhaps further down the road, the team is considering a population with frontotemporal dementia in Colombia where Kosik has conducted similar studies in Alzheimer’s disease.

Concepts Keywords
Albert Einstein Cognitive disorders
Brain Medicine
California Psychiatric diagnosis
Cancer Dementia
Carbon Branches of biology
Catalytic Drug targeting
Catalyzes Risk frontotemporal dementia
Clinical Trials Models frontotemporal dementia
Colombia Neurodegenerative diseases
Dementia Cuts
Emotion Causes frontotemporal dementia
Energy Alzheimers disease
Enzyme Energy
Everest Senescence
Farnesylation RTT
Frontotemporal Dementia Tau protein
Gene Tauopathy
Globe Neurofibrillary tangle
GTPase Frontotemporal dementia
GTPases Neuroscience
Harvard Stem cells
Inflammation
Interrupt
Membrane
Memory
Microtubule
Microtubules
Misfolding
Motor Skills
Mount Sinai
Mutation
Neurodegeneration
Neurodegenerative Disease
Neurodegenerative Diseases
Neurofibrillary Tangle
Neurofibrillary Tangles
Neuron
Neurons
Neuroscience
Neuroscientist
Pathology
Polish
Progeria
Protein
Railroad
Ras
RAS
Ras Superfamily
Santa Barbara
Stem Cells
Tangled
Temporal Lobes
Tumor
Uphill
Washington University

Semantics

Type Source Name
disease DOID progeria
disease MESH progeria
gene UNIPROT SET
gene UNIPROT AMACR
disease MESH inflammation
gene UNIPROT DDX53
drug DRUGBANK Dihydrotachysterol
gene UNIPROT RASD2
disease DOID neurodegenerative disease
drug DRUGBANK Rasagiline
disease MESH cancer
disease DOID cancer
gene UNIPROT SMIM10L2B
gene UNIPROT SMIM10L2A
gene UNIPROT SSRP1
drug DRUGBANK Activated charcoal
gene UNIPROT SIRPA
drug DRUGBANK Lonafarnib
gene UNIPROT SH3YL1
gene UNIPROT RAB35
disease MESH neurofibrillary tangle
disease MESH development
drug DRUGBANK Aducanumab
disease DOID frontotemporal dementia
pathway BSID Neurodegenerative Diseases
disease MESH frontotemporal dementia
disease MESH neurodegenerative diseases
disease DOID dementia
disease MESH dementia
gene UNIPROT MAPT

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *