2026-04-27T22:00:38Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/762542026-03-12T11:41:06Zcom_10324_1187com_10324_931com_10324_894col_10324_1408

00925njm 22002777a 4500 dc Fernández Peña, Laura author González Andrés, Paula author Tapias Molina, Victor author Núñez Llorente, Lucía author Villalobos Jorge, Carlos author 2023 Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neu rodegenerative diseases in the elderly. The key histopathological features of these diseases are the presence of abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain un known, but there is extensive evidence indicating that excessive generation of reactive oxygen speciesROS) and reactive nitrogen species (RNS), along with a depleted antioxidant system, mitochondrial dysfunction, and intracellular Ca2+ dyshomeostasis, plays a vital role in the pathophysiology of these neurological disorders. Due to an improvement in life expectancy, the incidence of age-related neurodegenerative diseases has significantly increased. However, there is no effective protective treatment or therapy available but rather only very limited palliative treatment. Therefore, there is an urgent need for the development of preventive strategies and disease-modifying therapies to treat AD/PD.Because dysregulated Ca2+ metabolism drives oxidative damage and neuropathology in these diseases, the identification or development of compounds capable of restoring Ca2+ homeostasis and signaling may provide a neuroprotective avenue for the treatment of neurodegenerative diseases. In addition, a set of strategies to control mitochondrial Ca2+ homeostasis and signaling has been reported, including decreased Ca2+ uptake through voltage-operated Ca2+ channels (VOCCs). In this article, we review the modulatory effects of several heterocyclic compounds on Ca2+ homeostasis and trafficking, as well as their ability to regulate compromised mitochondrial function and associated free-radical production during the onset and progression of AD or PD. This comprehensive review also describes the chemical synthesis of the heterocycles and summarizes the clinical trial outcomes. Antioxidants 2023, 12, 1282 https://uvadoc.uva.es/handle/10324/76254 https://doi.org/10.3390/antiox12061282 1282 12 Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer’s Disease and Parkinson’s Disease