Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder caused by degeneration of motor neurons. The cause for most cases of ALS is multi-factorial,this enhances the need to characterize and isolate specific biomarkers found in biological samples from ALS patients. To this end we use human mesenchymal stem cells (hMSC) derived from the bone marrow of six ALS patients (ALS hMSC) and identified two genes, Cytoplasmic FMR Interacting Protein 2 (CyFIP2) and Retinoblastoma (Rb) Binding Protein 9 (RbBP9) with a significant decrease in post transcriptional A to I RNA editing compared to hMSC of healthy individuals. At the transcriptional level we show abnormal expression of these two genes in ALS hMSC by quantitative real time-PCR (qRT-PCR) and Western blot suggesting a problem in the regulation of these genes in ALS. To strengthen this view we tested by qRT-PCR the expression of these genes in peripheral blood leukocytes (PBL) isolated from blood samples of 17 ALS patients and found that CyFIP2 and RbBP9 levels of expression were significantly different compared to the levels of expression of these two genes in 19 normal PBL samples. Altogether we found two novel ALS potential biomarkers in non-neural tissues from ALS patients that may have direct diagnostic and therapeutic implications to the disease.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord, brainstem and motor cortex, resulting in generalized weakness and muscle atrophy
Results human mesenchymal stem cells (hMSC) were isolated from bone marrow samples of 6 ALS patients (ALS hMSC) and from 6 non-ALS donors, based on their known property to adhere onto a plastic surface [19]
We have identified two genes Cytoplasmic FMR Interacting Protein 2 (CyFIP2) and RbBP9 that are differentially expressed in bone marrow derived hMSC and in peripheral blood leukocytes (PBL) of ALS patients
Summary
ALS is a fatal and incurable neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord, brainstem and motor cortex, resulting in generalized weakness and muscle atrophy. The causes for most cases of ALS are unknown and the clinical course is highly variable, suggesting that multiple factors underlie the disease mechanism [5]. This fact enhances the need to use a multidisciplinary approach to characterize and isolate specific biomarkers found in biological samples from ALS patients. To this end we use human mesenchymal stem cells (hMSC) derivedfrom the bone marrow of ALS patients and characterize their biological potential to identify ALS related biomarkers.
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