El dia 16 de desembre va presentar la seva tesi doctoral Marina Carrasco, dirigida pels Drs. Miren Ettcheto i Antoni Camins, amb el títol "La Licochalcona A com a Agent Neuroprotector: Estudi dels Mecanismes Farmacològics en Models Murins de Dèficit Cognitiu".

A continuació podeu llegir un breu resum de la tesi:

Dementia, such as Alzheimer’s Disease (AD), is the first leading cause of disability among people aged over 65 and the fourth leading cause of death in the European region. With the progressive aging of the global population, the burden of dementia and AD is expected to double by 2030. Despite extensive research, effective pharmacological therapies remain limited, primarily due to single target approaches and CNS limited strategies. The conceptual framework of neurodegenerative diseases is shifting toward a systemic perspective, emphasizing the interplay between hepatic dysfunction and brain pathology, with metabolism and inflammation emerging as key mediators. This highlights the need to identify novel multi-target compounds with neuroprotective properties that address the systemic nature of neurodegenerative processes.

In this context, Licochalcone A (LCA) is a chalcone-type flavonoid extracted from the root of Glycyrrhiza inflata, a plant commonly used in the Traditional Chinese Medicine for multiple purposes. This compound has demonstrated multiple therapeutic properties, including antidiabetic and anti-inflammatory effects. However, the neuroprotective mechanisms of LCA remain largely unexplored to date.

The present doctoral thesis provides an integrative analysis of the neuroprotective properties of LCA and its underlying pharmacological mechanisms across three complementary murine models of cognitive decline: LPS-induced neuroinflammation, high fat diet (HFD)-induced metabolic dysfunction, and APP/PS1 mice. Throughout all the experimental models LCA demonstrated to ameliorate memory impairment by modulating multiple interconnected mechanisms in both liver and brain.

From a mechanistic perspective, LCA demonstrated systemic anti-inflammatory effects by downregulating Tlr4 and reducing glial reactivity. Additionally, it enhanced antioxidant defenses and mitochondrial function. In parallel, LCA improved systemic glucose homeostasis by restoring insulin signaling through the modulation of the PI3K/AKT pathway and PTP1B activity. These neuroprotective effects were associated with enhanced Aβ clearance, leading to reduced levels of Aβ42 and plaque burden. Altogether, LCA preserved structural and functional synaptic plasticity by upregulating post-synaptic proteins and promoting BDNF signaling, ultimately leading to increased dendritic spine density.

Overall, the results of this doctoral thesis demonstrate that LCA effectively mitigates cognitive decline by simultaneously regulating inflammation, oxidative stress, metabolic dysfunction, amyloid burden, and synaptic plasticity. These findings position LCA as a promising therapeutic candidate with systemic and multi-target actions for the prevention of neurodegenerative disorders.