\ ALS Research \ Evidence for ALS as a disorder of RNA metabolism
Defects in RNA binding might represent a disease mechanism common to all cases of ALS, a leading Canadian researcher reports.
In a recent review published in the Journal of the Neurological Sciences, Michael Strong, MD, a clinician-scientist at University Hospital and the Robarts Research Institute in London, Ontario, suggests that altered regulation of RNA function by RNA-binding proteins might underlie the motor neuron degeneration observed in ALS and provide a mechanistic link between familial (hereditary) and sporadic cases.
Strong’s hypothesis is not new, but recently identified genetic mutations in ALS patients have provided compelling support. Mutations in genes such as TAR DNA-binding protein (TDP-43) and fused in liposarcoma (FUS) – which have been identified in both familial and sporadic cases of ALS – result in RNA binding defects, which means the protein products of the mutated genes interact with RNA differently than they normally would.
RNA is an intermediate between DNA – the genetic blueprint, and protein – the final product of that blueprint. Interference with the binding of RNA by proteins involved in processing, stabilizing, transporting or degrading it can lead to abnormal protein expression. This, in turn, can lead to disruptions in essential cellular functions.
Strong proposes that while the disease-initiating trigger might vary between patients, the pathway to motor neuron death is the same.
Strong is confident that future studies examining how RNA-binding proteins regulate RNA function will shed light on the disease process in ALS. This hypothesis also opens the door to novel treatment strategies, Strong reports.
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Evidence for ALS as a disorder of RNA metabolism
By: Katie Moisse, PhDDefects in RNA binding might represent a disease mechanism common to all cases of ALS, a leading Canadian researcher reports.
In a recent review published in the Journal of the Neurological Sciences, Michael Strong, MD, a clinician-scientist at University Hospital and the Robarts Research Institute in London, Ontario, suggests that altered regulation of RNA function by RNA-binding proteins might underlie the motor neuron degeneration observed in ALS and provide a mechanistic link between familial (hereditary) and sporadic cases.
Strong’s hypothesis is not new, but recently identified genetic mutations in ALS patients have provided compelling support. Mutations in genes such as TAR DNA-binding protein (TDP-43) and fused in liposarcoma (FUS) – which have been identified in both familial and sporadic cases of ALS – result in RNA binding defects, which means the protein products of the mutated genes interact with RNA differently than they normally would.
RNA is an intermediate between DNA – the genetic blueprint, and protein – the final product of that blueprint. Interference with the binding of RNA by proteins involved in processing, stabilizing, transporting or degrading it can lead to abnormal protein expression. This, in turn, can lead to disruptions in essential cellular functions.
Strong proposes that while the disease-initiating trigger might vary between patients, the pathway to motor neuron death is the same.
Strong is confident that future studies examining how RNA-binding proteins regulate RNA function will shed light on the disease process in ALS. This hypothesis also opens the door to novel treatment strategies, Strong reports.
| Posted On: Thursday, January 07, 2010 Modified: Thursday, January 07, 2010 Category: ALS Research Posted By: |