RESUMEN
Klotho is recognized as an aging-suppressor protein that is implicated in a variety of processes and signaling pathways. The anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-tumor bioactivities of klotho have extended its application in neurosciences and made the protein popular for its lifespan-extending capacity. Furthermore, it has been demonstrated that klotho levels would reduce with aging and numerous pathologies, particularly those related to the central nervous system (CNS). Evidence supports the idea that klotho can be a key therapeutic target in CNS diseases such as amyotrophic lateral sclerosis, Parkinson's disease, stroke, and Alzheimer's disease. Reviewing the literature suggests that the upregulation of klotho expression regulates various signaling pathways related to autophagy, oxidative stress, inflammation, cognition, and ferroptosis in neurological disorders. Therefore, it has been of great interest to develop drugs or agents that boost or restore klotho levels. In this regard, the present review was designed and aimed to gather the delegated documents regarding the therapeutic potential of Klotho in CNS diseases focusing on the molecular and cellular mechanisms.
Asunto(s)
Enfermedades del Sistema Nervioso Central , Proteínas Klotho , Transducción de Señal , Humanos , Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Animales , Estrés Oxidativo , Glucuronidasa/metabolismo , Glucuronidasa/genética , Autofagia , Envejecimiento/metabolismo , Envejecimiento/genéticaRESUMEN
Sleep deprivation (SD) induces learning and memory deficits via inflammatory responses and oxidative stress. On the other hand, sericin (Ser) possesses potent antioxidant and neuroprotective effects. We investigated the effect of different doses of Ser on the SD-induced cognitive impairment. Ser (100, 200, and 300 mg/kg) was administered to animals via oral gavage for 8 days, 5 days before to SD, and during SD. SD was induced in mice using a modified multiple platform model, starting on the 6th day for 72 h. Spatial learning and memory were assessed using the Lashley III maze. Serum corticosterone level, and hippocampal malondialdehyde (MDA), total antioxidant capacity (TAC), and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were evaluated. The expression of growth-associated protein 43 (GAP-43), post-synaptic density-95 (PSD-95), synapsin 1 (SYN-1), and synaptophysin (SYP), and inflammation markers were detected by western blotting. SD caused cognitive impairment, while Ser pretreatment prevented such an effect. Serum corticosterone also increased with SD, but its levels were suppressed in SD mice receiving Ser. Furthermore, Ser normalized SD-induced reduction in the hippocampus activity of SOD and GPx, increased TAC, and decreased MDA levels. Besides, Ser pretreatment increased GAP-34, SYP, SYN-I, and PSD-95 and reduced IL1-ß and TNF-α in the hippocampus. SD induced memory impairment and pretreatment with Ser improved memory via its antioxidant, anti-inflammation, and up-regulation of synaptic proteins in the hippocampus.