Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and neurodegeneration.Aging is considered the major risk factor for Parkinson’s and Alzheimer’s disease develops.Likewise,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders.Currently,no treatment can effectively reverse these neurodegenerative pathologies.However,some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes.In the previous framework,Vanadium species have demonstrated a notable antidiabetic effect.Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome.The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms.This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

IL-1β, TNF-α and Sambucus nigra Reactive Serum Proteins as Biomarkers of Mild Cognitive Impairment and Alzheimer Disease Progression

Amyloid-β (Aβ) can induce a chronic inflammatory immune response that is associated, amongst many others, to abnormal glycosylation, inducible nitric oxide synthase (iNOS) and nitric oxide (NO). The relation between development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease progression and these serum markers has not been evaluated. Serum levels of iNOs, NO, TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 are determined with commercially available kits. Sialylation of albumin-free serum patterns is determined by Western blot analysis with Sambucus nigra (specific for sialic acid attached to terminal galactose in α2,6 linkage) lectin. Apolipoprotein E (ApoE) haplotype is determined by Western blot using specific anti-ApoE 2, 3 or 4 antibodies. A mini-mental state examination (MMSE) test is also performed in the 10 MCI patients, 19 Alzheimer’s disease (AD) patients and 46 healthy age-matched controls evaluated. The results show an increase of iNOS in MCI and AD but significantly higher NO concentrations are only found in MCI patients. TNF-α and IL-1β concentrations are the only significantly increased cytokines in MCI patients;no differences between control and MCI or AD patients are found in regard to the other cytokines. An abnormal MMSE test result only correlates with a decrease in serum NO concentration in MCI patients. The terminal sialic acid linkage pattern of serum proteins also shows highly significant differences between MCI and AD patient. ApoE3/4 or 4/4 haplotypes are characteristic of MCI and AD patients. Our results imply that increased serum TNF-α, IL-1β, iNOS, NO and alterations of serum proteins glycosylation patterns in adult individuals with an abnormal MMSE test may serve as an early biomarker of MCI and AD development.