RESUMO
Anandamide (AEA) analogs show fair effects in counteracting the deterioration of Alzheimer's disease (AD). Our previous studies demonstrated that AEA analog-N-linoleyltyrosine (NITyr) exerted significant activities. In our current research, the role and mechanisms of NITyr were assessed in APP/PS1 mice mimicking the AD model. NITyr improved motor coordination in the rotarod test (RRT) and ameliorated spatial memory in the Morris water maze (MWM) but did not increase spontaneous locomotor activity in the open field test (OFT). In addition, NITyr protected neurons against ß-amyloid (Aß) injury via hematoxylin-eosin (HE) and Nissl staining. Moreover, the related biochemical indexes showed that NITyr reduced the levels of Aß40 and Aß42 in the hippocampus but did not affect the expression of p-APP and ß-secretase 1 (BACE1). Furthermore, the autophagy inhibitor 3-methyladenine (3 MA) attenuated the effect of NITyr on animal behaviors and neurons. Meanwhile, NITyr upregulated the expression levels of LC3-II and Beclin-1, which were weakened by AM630 (an antagonist of CB2 receptor and a weak partial agonist of CB1 receptors). AM630 also weakened the role of NITyr in animal behaviors. Thus, NITyr improved behavioral impairment and neural loss by inducing autophagy mainly mediated by the CB2 receptor, and weakly mediated by the CB1 receptor.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Autofagia/efeitos dos fármacos , Fármacos Neuroprotetores , Receptor CB2 de Canabinoide/metabolismo , Tirosina/análogos & derivados , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Animais , Modelos Animais de Doenças , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1 , Desempenho Psicomotor/efeitos dos fármacos , Receptor CB1 de Canabinoide/metabolismo , Receptores de Canabinoides , Memória Espacial/efeitos dos fármacos , Tirosina/farmacologiaRESUMO
Astrocytes are key targets for treating cerebral ischemia in the central nervous system. Non-coding RNAs (ncRNAs) participate in the pathological processes of astrocytes in cerebral ischemia. Recent reports suggest that ncRNAs ameliorate the outcome of cerebral ischemia by mediating astrocytes' inflammatory reaction, oxidative stress, excitotoxicity, autophagy, and apoptosis. Reconstructing cellular systems might offer a promising strategy for treating cerebral ischemia. This review briefly discusses the potential of ncRNAs as drug targets and explores the molecular regulatory mechanisms through which ncRNAs target astrocytes in cerebral ischemia. It provides an overview of the current research, discusses ncRNAs' implications as clinical markers for cerebral ischemia, and anticipates that ongoing research on ncRNAs may contribute to novel therapeutic approaches for treating this condition.