RNDr. Lenka Maletínská, CSc., Institute of Organic Chemistry and Biochemistry of the CAS
As the population progressively ages, the prevalence of obesity, its metabolic complications, and neurodegenerative diseases continue to rise. Current data suggest that obesity and related insulin resistance, leptin resistance and type 2 diabetes mellitus (T2DM) significantly contribute to several age-associated neurodegenerative disorders such as Alzheimer’s disease (AD). The combination of increasing prevalence of obesity, T2DM and aging calls for novel approaches able to prevent or postpone the onset of neurodegenerative diseases or to slow their progression. At present, no effective treatment for obesity or AD is available. Nevertheless, a possible new strategy for the prevention/treatment of neurodegenerative diseases has emerged. Drugs initially developed for treatment of T2DM showed beneficial effects also in animal models of AD.
In our group, we have designed lipidized analogs of anorexigenic neuropeptide prolactin-releasing peptide (PrRP), which is involved in energy balance regulation, and might be promising candidate for treatment of obesity. Diet induced obese mice and rats, as well as APP/PS1 mice with neurodegeneration were treated repeatedly with palmitoylated PrRP analog and body weight, metabolic parameters as well as hypothalamic signaling and neurodegeneration in hippocampi were followed. Lipidized PrRP analog showed lowering effect on food intake, body weight and improvement of metabolic parameters in diet-induced obese mice and rats. In addition, it decreased two features of AD, Abeta plaques and Tau hyperphosphorylation and improved neuroinflammation in APP/PS1 mice.
Lipidized analogs of PrRP are candidates for possible treatment of obesity and T2DM. Moreover, they have a potential to improve neurodegenerative disorders.
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