Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe?
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a massive neuroinflammatory reaction, which plays a key role in the progression of the disease. One of the major mediators of the inflammatory response is the pleiotropic cytokine tumor necrosis factor α (TNFα)...
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MDPI AG
2021-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/3/518 |
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| author | Giulia Guidotti Chiara Scarlata Liliana Brambilla Daniela Rossi |
| author_facet | Giulia Guidotti Chiara Scarlata Liliana Brambilla Daniela Rossi |
| author_sort | Giulia Guidotti |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a massive neuroinflammatory reaction, which plays a key role in the progression of the disease. One of the major mediators of the inflammatory response is the pleiotropic cytokine tumor necrosis factor α (TNFα), mainly released within the central nervous system (CNS) by reactive astrocytes and microglia. Increased levels of TNFα and its receptors (TNFR1 and TNFR2) have been described in plasma, serum, cerebrospinal fluid and CNS tissue from both ALS patients and transgenic animal models of disease. However, the precise role exerted by TNFα in the context of ALS is still highly controversial, since both protective and detrimental functions have been reported. These opposing actions depend on multiple factors, among which includes the type of TNFα receptor activated. In fact, TNFR2 seems to mediate a harmful role being involved in motor neuron cell death, whereas TNFR1 signaling mediates neuroprotective effects, promoting the expression and secretion of trophic factors. This suggests that a better understanding of the cytokine impact on ALS progression may enable the development of effective therapies aimed at strengthening the protective roles of TNFα and at suppressing the detrimental ones. |
| first_indexed | 2024-03-09T06:06:48Z |
| format | Article |
| id | doaj.art-e7cf45efe1a348b4a65c3a8f8ed66794 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T06:06:48Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-e7cf45efe1a348b4a65c3a8f8ed667942023-12-03T12:03:17ZengMDPI AGCells2073-44092021-03-0110351810.3390/cells10030518Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe?Giulia Guidotti0Chiara Scarlata1Liliana Brambilla2Daniela Rossi3Laboratory for Research on Neurodegenerative Disorders, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, ItalyLaboratory for Research on Neurodegenerative Disorders, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, ItalyLaboratory for Research on Neurodegenerative Disorders, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, ItalyLaboratory for Research on Neurodegenerative Disorders, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, ItalyAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a massive neuroinflammatory reaction, which plays a key role in the progression of the disease. One of the major mediators of the inflammatory response is the pleiotropic cytokine tumor necrosis factor α (TNFα), mainly released within the central nervous system (CNS) by reactive astrocytes and microglia. Increased levels of TNFα and its receptors (TNFR1 and TNFR2) have been described in plasma, serum, cerebrospinal fluid and CNS tissue from both ALS patients and transgenic animal models of disease. However, the precise role exerted by TNFα in the context of ALS is still highly controversial, since both protective and detrimental functions have been reported. These opposing actions depend on multiple factors, among which includes the type of TNFα receptor activated. In fact, TNFR2 seems to mediate a harmful role being involved in motor neuron cell death, whereas TNFR1 signaling mediates neuroprotective effects, promoting the expression and secretion of trophic factors. This suggests that a better understanding of the cytokine impact on ALS progression may enable the development of effective therapies aimed at strengthening the protective roles of TNFα and at suppressing the detrimental ones.https://www.mdpi.com/2073-4409/10/3/518amyotrophic lateral sclerosistumor necrosis factor alphaneuroinflammationmotor neuron degenerationrehabilitation |
| spellingShingle | Giulia Guidotti Chiara Scarlata Liliana Brambilla Daniela Rossi Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe? Cells amyotrophic lateral sclerosis tumor necrosis factor alpha neuroinflammation motor neuron degeneration rehabilitation |
| title | Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe? |
| title_full | Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe? |
| title_fullStr | Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe? |
| title_full_unstemmed | Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe? |
| title_short | Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe? |
| title_sort | tumor necrosis factor alpha in amyotrophic lateral sclerosis friend or foe |
| topic | amyotrophic lateral sclerosis tumor necrosis factor alpha neuroinflammation motor neuron degeneration rehabilitation |
| url | https://www.mdpi.com/2073-4409/10/3/518 |
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