Scientists discover novel mechanism underlying ALS and related dementia
Northwestern Medicine News Sep 28, 2017
A multi-organization team of scientists has discovered a novel mechanism for how a gene mutation leads to the death of neurons in amyotrophic lateral sclerosis (ALS) and the related disease frontotemporal dementia (FTD), findings which could inform the development of new treatments.
The study, published in the journal Neuron, was co-authored by Sandra Weintraub, PhD, professor of Psychiatry and Behavioral Sciences and of Neurology; Marsel Mesulam, MD, director of the Cognitive Neurology and AlzheimerÂs Disease Center and chief of Behavioral Neurology in the Department of Neurology; and Eileen Bigio, MD, Paul E. Steiner Research Professor of Pathology.
In some cases, patients with ALS also present with FTD, a type of dementia with overlapping pathologic and genetic characteristics.
In the current study, the scientists were able to link mutations in the gene that encodes the protein TIA1 to the development of both ALS and FTD.
The team demonstrated that the faulty protein disrupted the normal disassembly of stress granules  dense aggregations of proteins and RNA that form under stress conditions  and promoted their accumulation in neurons. The stress granules were found to contain TDP-43, a protein previously implicated in ALS and FTD pathology. Further, when TIA1 was mutated, TDP-43 contained in stress granules also became less mobile and more insoluble.
This accumulation led to the death of neurons in the brain and spinal cord that control muscles in ALS, and the death of neurons in the brain in FTD.
The research, by identifying a novel cellular malfunction driving ALS and FTD, may offer scientists a new pathway towards the development of treatment for both disorders.
Go to Original
The study, published in the journal Neuron, was co-authored by Sandra Weintraub, PhD, professor of Psychiatry and Behavioral Sciences and of Neurology; Marsel Mesulam, MD, director of the Cognitive Neurology and AlzheimerÂs Disease Center and chief of Behavioral Neurology in the Department of Neurology; and Eileen Bigio, MD, Paul E. Steiner Research Professor of Pathology.
In some cases, patients with ALS also present with FTD, a type of dementia with overlapping pathologic and genetic characteristics.
In the current study, the scientists were able to link mutations in the gene that encodes the protein TIA1 to the development of both ALS and FTD.
The team demonstrated that the faulty protein disrupted the normal disassembly of stress granules  dense aggregations of proteins and RNA that form under stress conditions  and promoted their accumulation in neurons. The stress granules were found to contain TDP-43, a protein previously implicated in ALS and FTD pathology. Further, when TIA1 was mutated, TDP-43 contained in stress granules also became less mobile and more insoluble.
This accumulation led to the death of neurons in the brain and spinal cord that control muscles in ALS, and the death of neurons in the brain in FTD.
The research, by identifying a novel cellular malfunction driving ALS and FTD, may offer scientists a new pathway towards the development of treatment for both disorders.
Only Doctors with an M3 India account can read this article. Sign up for free or login with your existing account.
4 reasons why Doctors love M3 India
-
Exclusive Write-ups & Webinars by KOLs
-
Daily Quiz by specialty
-
Paid Market Research Surveys
-
Case discussions, News & Journals' summaries