6533b85dfe1ef96bd12bea11
RESEARCH PRODUCT
Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα
Caterina BendottiMassimo TortaroloMichael J. StrongDaniele Lo CocoDaniele Lo CocoAntonio VallarolaGabriella MarconGabriella MarconM. PoloniEleonora AronicaMaria Teresa GiordanaPietro VeglianeseEttore BeghiAnand Iyersubject
0301 basic medicinePathologymedicine.medical_specialtyAmyotrophic Lateral Sclerosis; Animals; Humans; Motor Neurons; T-Lymphocytes Regulatory; Tumor Necrosis Factor-alphamedicine.medical_treatmentT-LymphocytesCentral nervous systemImmunologyAmyotrophic lateral sclerosis inflammation TNFαInflammationReview ArticleT-Lymphocytes Regulatory03 medical and health sciences0302 clinical medicineImmune systemCerebrospinal fluidImmunology; Cell BiologyTNFαlcsh:PathologyMedicineAnimalsHumansAmyotrophic lateral sclerosisMotor Neuronsbusiness.industryTumor Necrosis Factor-alphaAmyotrophic Lateral SclerosisCell BiologyMotor neuronmedicine.diseaseRegulatory3. Good health030104 developmental biologymedicine.anatomical_structureCytokineinflammationImmunologyTumor necrosis factor alphamedicine.symptombusiness030217 neurology & neurosurgerylcsh:RB1-214description
Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFαis one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFαlevels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear. Our group and others have recently reported opposite involvements of TNFR1 and TNFR2 in motor neuron death. TNFR2 mediates TNFαtoxic effects on these neurons presumably through the activation of MAP kinase-related pathways. On the other hand, TNFR2 regulates the function and proliferation of regulatory T cells (Treg) whose expression is inversely correlated with the disease progression rate in ALS patients. In addition, TNFαis considered a procachectic factor with a direct catabolic effect on skeletal muscles, causing wasting. We review and discuss the role of TNFαin ALS in the light of its multisystem nature.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-09-01 |