Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA
Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases which are characterized by the loss of motoneurons within the central nervous system. SMA is a monogenic disease caused by reduced levels of the Survival of motoneuron protein, whereas ALS is a multi...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-03-01
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| Series: | Neuroscience Insights |
| Online Access: | https://doi.org/10.1177/26331055221087740 |
| _version_ | 1811311768921702400 |
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| author | Sabrina Kubinski Peter Claus |
| author_facet | Sabrina Kubinski Peter Claus |
| author_sort | Sabrina Kubinski |
| collection | DOAJ |
| description | Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases which are characterized by the loss of motoneurons within the central nervous system. SMA is a monogenic disease caused by reduced levels of the Survival of motoneuron protein, whereas ALS is a multi-genic disease with over 50 identified disease-causing genes and involvement of environmental risk factors. Although these diseases have different causes, they partially share identical phenotypes and pathomechanisms. To analyze and identify functional connections and to get a global overview of altered pathways in both diseases, protein network analyses are commonly used. Here, we used an in silico tool to test for functional associations between proteins that are involved in actin cytoskeleton dynamics, fatty acid metabolism, skeletal muscle metabolism, stress granule dynamics as well as SMA or ALS risk factors, respectively. In network biology, interactions are represented by edges which connect proteins (nodes). Our approach showed that only a few edges are necessary to present a complex protein network of different biological processes. Moreover, Superoxide dismutase 1, which is mutated in ALS, and the actin-binding protein profilin1 play a central role in the connectivity of the aforementioned pathways. Our network indicates functional links between altered processes that are described in either ALS or SMA. These links may not have been considered in the past but represent putative targets to restore altered processes and reveal overlapping pathomechanisms in both diseases. |
| first_indexed | 2024-04-13T10:24:43Z |
| format | Article |
| id | doaj.art-192f0e0f9f1f458eb63ab4f5a0016108 |
| institution | Directory Open Access Journal |
| issn | 2633-1055 |
| language | English |
| last_indexed | 2024-04-13T10:24:43Z |
| publishDate | 2022-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Neuroscience Insights |
| spelling | doaj.art-192f0e0f9f1f458eb63ab4f5a00161082022-12-22T02:50:21ZengSAGE PublishingNeuroscience Insights2633-10552022-03-011710.1177/26331055221087740Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMASabrina Kubinski0Peter Claus1Center for Systems Neuroscience (ZSN), Hannover, GermanySMATHERIA gGmbH – Non-Profit Biomedical Research Institute, Hannover, GermanySpinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases which are characterized by the loss of motoneurons within the central nervous system. SMA is a monogenic disease caused by reduced levels of the Survival of motoneuron protein, whereas ALS is a multi-genic disease with over 50 identified disease-causing genes and involvement of environmental risk factors. Although these diseases have different causes, they partially share identical phenotypes and pathomechanisms. To analyze and identify functional connections and to get a global overview of altered pathways in both diseases, protein network analyses are commonly used. Here, we used an in silico tool to test for functional associations between proteins that are involved in actin cytoskeleton dynamics, fatty acid metabolism, skeletal muscle metabolism, stress granule dynamics as well as SMA or ALS risk factors, respectively. In network biology, interactions are represented by edges which connect proteins (nodes). Our approach showed that only a few edges are necessary to present a complex protein network of different biological processes. Moreover, Superoxide dismutase 1, which is mutated in ALS, and the actin-binding protein profilin1 play a central role in the connectivity of the aforementioned pathways. Our network indicates functional links between altered processes that are described in either ALS or SMA. These links may not have been considered in the past but represent putative targets to restore altered processes and reveal overlapping pathomechanisms in both diseases.https://doi.org/10.1177/26331055221087740 |
| spellingShingle | Sabrina Kubinski Peter Claus Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA Neuroscience Insights |
| title | Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA |
| title_full | Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA |
| title_fullStr | Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA |
| title_full_unstemmed | Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA |
| title_short | Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA |
| title_sort | protein network analysis reveals a functional connectivity of dysregulated processes in als and sma |
| url | https://doi.org/10.1177/26331055221087740 |
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