Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights.

Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood-brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.

Abscisic acid prevents pollen abortion under high-temperature stress by mediating sugar metabolism in rice spikelets.

Heat stress at the pollen mother cell (PMC) meiotic stage leads to pollen sterility in rice, in which the reactive oxygen species (ROS) and sugar homeostasis are always adversely affected. This damage is reversed by abscisic acid (ABA), but the mechanisms underlying the interactions among the ABA, sugar metabolism, ROS and heat shock proteins in rice spikelets under heat stress are unclear. Two rice genotypes, Zhefu802 (a recurrent parent) and fgl (its near-isogenic line) were subjected to heat stress of 40°C after pre-foliage sprayed with ABA and its biosynthetic inhibitor fluridone at the meiotic stage of PMC. The results revealed that exogenous application of ABA reduced pollen sterility caused by heat stress. This was achieved through various means, including: increased levels of soluble sugars, starch and non-structural carbohydrates, markedly higher relative expression levels of heat shock proteins (HSP24.1 and HSP71.1) and genes related to sugar metabolism and transport, such as sucrose transporters (SUT) genes, sucrose synthase (SUS) genes and invertase (INV) genes as well as increased antioxidant activities and increased content of adenosine triphosphate and endogenous ABA in spikelets. In short, exogenous application of ABA prior to heat stress enhanced sucrose transport and accelerated sucrose metabolism to maintain the carbon balance and energy homeostasis, thus ABA contributed to heat tolerance in rice.