Introduction: At present, cholinesterase inhibitors constitute the basis for therapy of Alzheimer's disease (AD); these drugs were rationally introduced given the loss of central cholinergic neurotransmission, even though there are many other systems affected in AD, including glutamatergic pathway.
Development: In addition to the loss of central cholinergic neurotransmission, biochemical evidence suggests glutamatergic dysfunction in AD and thus, therapeutic strategies directed at the glutamatergic system may be useful. These drugs include milacemide, cicloserine and ampakines (positive modulation) and memantine (negative modulation). Lithium seems to be a promising agent in AD, although the mechanism of action is poorly understood. Finally anti-inflammatory agents may be another therapeutic approach to AD.
Conclusion: In addition to drugs acting on the cholinergic system, a large number of drugs with different mechanism could be used for the treatment and prevention of AD.
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Metab Brain Dis
January 2025
Hepato-Neuro Laboratory, Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, 900, Rue Saint-Denis - Pavillon R, R08.422, Montréal (Québec), H2X 0A9, Canada.
Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD.
View Article and Find Full Text PDFProteomes
January 2025
Instituto de Matemática e Estatística, Departamento de Ciência da Computação, Universidade de São Paulo, Rua do Matão 1010, São Paulo 05508-090, SP, Brazil.
The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by lipid peroxidation. Post-translational modifications of p53 generate proteoforms that significantly enhance its functional diversity in regulating these mechanisms.
View Article and Find Full Text PDFAudiol Res
December 2024
ENT & Audiology Unit, Department of Neurosciences, University Hospital of Ferrara, 44124 Ferrara, Italy.
Objectives: The present study aims to identify potential predictive factors for developing sensorineural hearing loss (SNHL) in individuals with congenital Cytomegalovirus (cCMV) infection.
Methods: A retrospective study was performed on 50 subjects with cCMV infection (symptomatic and asymptomatic), followed at the Audiology Service of Sant'Anna Hospital (University Hospital of Ferrara). The following data were analyzed: the type of maternal Cytomegalovirus (CMV) infection (primary versus non-primary), time of in utero infection, systemic signs and symptoms or laboratory test anomalies due to cCMV infection, and signs and symptoms of central nervous system (CNS) involvement at birth.
J Am Heart Assoc
January 2025
The Center for Vascular Disease and Translational Medicine, The Third Xiangya Hospital Central South University Changsha Hunan China.
Background: Pulmonary arterial hypertension (PAH) is an incurable disease initiated by endothelial dysfunction, secondary to vascular inflammation and occlusive pulmonary arterial vascular remodeling, resulting in elevated pulmonary arterial pressure and right heart failure. Previous research has reported that dysfunction of type 2 bone morphogenetic protein receptor (BMPR2) signaling pathway in endothelium is inclined to prompt inflammation in PAH models, but the underlying mechanism of BMPR2 deficiency-mediated inflammation needs further investigation. This study was designed to investigate whether BMPR2 deficiency contributes to pulmonary arterial hypertension via the NLRP3 (NOD-like receptor family protein 3)/GSDME (gasdermin E)-mediated pyroptosis pathway.
View Article and Find Full Text PDFFront Psychiatry
January 2025
Department of Infection Management, Wuxi No.2 People's Hospital (Jiangnan University Medical Center), Wuxi, China.
Objective: In this study, we examine the network structure of posttraumatic stress disorder (PTSD), including core symptoms and strong edges in patients undergoing chemotherapy for colorectal cancer in China, and lay the groundwork for targeted psychological interventions for these patients.
Methods: This study included 360 colorectal cancer patients receiving chemotherapy at a third-class hospital in Wuxi, China, from November 2023 to June 2024. The severity of each item of PTSD was assessed using the DSM-5 Checklist (PCL-5).
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