RESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the loss of upper and lower motor neurons (MNs) in the cerebral cortex, brainstem and spinal cord, with consequent weakness, atrophy and the progressive paralysis of all muscles. There is currently no medical cure, and riluzole and edaravone are the only two known approved drugs for treating this condition. However, they have limited efficacy, and hence there is a need to find new molecules. Dutasteride, a dual inhibitor of type 1 and type 2 5α-reductase (5AR) enzymes, the therapeutic purposes of which, to date, are the treatment of benign prostatic hyperplasia and androgenic alopecia, shows great anti-ALS properties by the molecular-topology methodology. Based on this evidence, this review aims to assess the effects of dutasteride on testosterone (T), progesterone (PROG) and 17ß-estradiol (17BE) as a therapeutic alternative for the clinical improvement of ALS, based on the hormonal, metabolic and molecular pathways related to the pathogenesis of the disease. According to the evidence found, dutasteride shows great neuroprotective, antioxidant and anti-inflammatory effects. It also appears effective against glutamate toxicity, and it is capable of restoring altered dopamine activity (DA). These effects are achieved both directly and through steroid hormones. Therefore, dutasteride seems to be a promising molecule for the treatment of ALS, although clinical studies are required for confirmation.
RESUMEN
(1) Background: Multiple sclerosis (MS) is a neurodegenerative disease characterized by pronounced inflammation. Interleukin 6 (IL-6) is an accurate marker for the state of inflammation, due to the high levels of this cytokine linked to the pathogenesis of the disease. These IL-6 levels could be lowered with an adequate dietary intake of vitamin D. The objective of the study was to determine the level of vitamin D ingested in a sample of patients with MS in the Valencian region (Spain), to establish the vitamin sources, and the possible link between the intake of vitamin D and the pathogenesis of the disease through a relationship with the level of IL-6. (2) Materials and Methods: A descriptive pilot study was carried out with 39 patients with MS in the Valencian region. The dietary-nutritional anamnesis was gained through the food frequency questionnaire (FFQ) and a food diary. Diet and eating habits were analyzed through the Easy Diet (version: 2.0.1)-Consultation Management Program® software, and IL-6 levels in blood by ELISA technique. (3) Results: The results show a low intake of vitamin D, which is significantly and negatively related to the intake of proteins of vegetable origin, which are consumed in less quantity than proteins of animal origin, and significantly and negatively related with the high blood levels of IL-6, possibly as a consequence of the high intake of fats, mainly unsaturated. (4) Conclusions: MS patients in the Valencian region ingest little vitamin D related to low intake of vegetable protein, which would explain the high levels of IL-6 linked to the high intake of mainly saturated fats.
RESUMEN
The relationship between gut microbiota and neurodegenerative diseases is becoming clearer. Among said diseases amyotrophic lateral sclerosis (ALS) stands out due to its severity and, as with other chronic pathologies that cause neurodegeneration, gut microbiota could play a fundamental role in its pathogenesis. Therefore, polyphenols could be a therapeutic alternative due to their anti-inflammatory action and probiotic effect. Thus, the objective of our narrative review was to identify those bacteria that could have connection with the mentioned disease (ALS) and to analyze the benefits produced by administering polyphenols. Therefore, an extensive search was carried out selecting the most relevant articles published between 2005 and 2020 on the PubMed and EBSCO database on research carried out on cell, animal and human models of the disease. Thereby, after selecting, analyzing and debating the main articles on this topic, the bacteria related to the pathogenesis of ALS have been identified, among which we can positively highlight the presence mainly of Akkermansia muciniphila, but also Lactobacillus spp., Bifidobacterium spp. or Butyrivibrio fibrisolvens. Nevertheless, the presence of Escherichia coli or Ruminococcus torques stand out negatively for the disease. In addition, most of these bacteria are associated with molecular changes also linked to the pathogenesis of ALS. However, once the main polyphenols related to improvements in any of these three ALS models were assessed, many of them show positive results that could improve the prognosis of the disease. Nonetheless, epigallocatechin gallate (EGCG), curcumin and resveratrol are the polyphenols considered to show the most promising results as a therapeutic alternative for ALS through changes in microbiota.
