Galectins are a group of β-galactoside-binding lectins associated with regulating immunological response. In the brains of AD patients and 5xFAD (familial AD) mice, galectin-3 (Gal-3) was highly upregulated and found to be expressed in microglia associated with Aβ plaques. However, the participation of other galectins, specifically galectin-9 (Gal-9) and T-cell immunoglobulin and mucin domain 3 (Tim-3) receptors, are unknown in the inflammatory response. The experimental model of the Aβ_25-35 peptide will allow us to study the mechanisms of neuroinflammation and describe the changes in the expression of the Gal-9 and Tim-3 receptor. This study aimed to evaluate whether Aβ_25-35 peptide administration into the lateral ventricles of rats upregulated Gal-9 and Tim-3 implicated in the modulation of neuroinflammation. The vehicle or Aβ_25-35 peptide (1 μg/μL) was bilaterally administered into the lateral ventricles of the rat, and control group. After the administration of the Aβ_25-35 peptide, animals were tested for learning (day 29) and spatial memory (day 30) in the novel object recognition test (NOR). On day 31, hippocampus was examined for morphological changes by Nilss stain, biochemical changes by NO₂ and MDA, immunohistochemical analysis by astrocytes (GFAP), microglia (Iba1), Gal-9 and Tim-3, and western blot. Our results show the administration of the Aβ_25-35 peptide into the lateral ventricles of rats induce memory impairment in the NOR by increases the oxidative stress and inflammatory response. This result is associated with an upregulation of Gal-9 and Tim-3 predominantly detected in the microglia cells of Aβ_25-35-treated rats with respect to the control group. Gal-9 and Tim-3 are upregulated in activated microglia that could modulate the inflammatory response and damage in neurodegenerative processes induced by the Aβ_25-35 peptide. Therefore, we suggest that Gal-9 and Tim-3 participate in the inflammatory process induced by the administration of the Aβ_25-35 peptide.

Epidemiological and clinical research on neurodegenerative diseases has shown that metabolic dysregulations increase the risk of developing Alzheimer’s Disease (AD). Many metabolic changes can be grouped into metabolic syndrome (MetS), which is defined as the presence of three or more risk factors, including insulin resistance, hyperglycemia, hypertension, central obesity, and dyslipidemia. These changes cause systemic effects that are crucial in triggering neuroinflammation and neurodegeneration, key factors in AD development. All these factors impair energy metabolism in peripheral tissues and the brain by decreasing glucose utilization, leading to alterations in O-GlcNAcylation, glycosylation, mitochondrial function, oxidative stress, chronic inflammation, synaptic dysfunction, autophagy impairment, and blood–brain barrier (BBB) dysfunction. However, these factors are modified and largely influenced by lifestyle choices. A newer perspective emphasizes that regular exercise is vital for maintaining brain metabolism as we age. Current evidence suggests that engaging in physical activity for individuals with metabolic syndrome reduces their risk of Alzheimer’s disease, enhances prognosis, and improves cognitive abilities. This review explores how metabolic syndrome relates to Alzheimer’s and highlights possible strategies for prevention and treatment.

Epidemiological and clinical research on neurodegenerative diseases have indicated that metabolic dysregulations increase the risk of developing Alzheimer's Disease (AD). Many metabolic alterations can be grouped within the metabolic syndrome (MetS), defined as the coexistence of three or more risk factors, such as insulin resistance, hyperglycemia, hypertension, central obesity, and dyslipidemia. These changes induce a systemic change that plays a critical role in inducing neuroinflammation and neurodegeneration as essential causes of AD pathogenesis. All these factors compromise peripheral tissues and brain energy metabolism through reduced glucose utilization, which contributes to alterations in O-GlcNAcylation, glycosylation, mitochondrial dysfunction, oxidative stress, chronic inflammation, synaptic dysfunction, impaired autophagy, and blood-brain barrier (BBB) dysfunction. However, these factors are modifiable elements that depend on lifestyle. A relatively new perspective proposes that exercise regularly plays an essential role in maintaining brain metabolism in ageing. Physical activity in MetS decreases the risk of developing Alzheimer's disease, is associated with better prognosis, and positively affects cognitive function in those patients. In this review, we discuss the mechanisms involved in MetS and their implication in AD and identify potential areas for preventive and therapeutic interventions.