Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is of importance in understanding the neuropathological progression of Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular deposits of the amyloid β-peptide (Aβ) and intraneuronal aggregates of the microtubule-associated protein tau. Critical roles of Aβ oligomer deposited and ganglioside GM1 could be formed as "seed" from insoluble GAβ polymer in initiating the pathogenic process, while tau might also mediate SPLs and their toxicity. The interaction between ceramide and α-Synuclein (α-Syn) accelerates the aggregation of ferroptosis and exacerbates the pathogenesis of AD. For instance, reducing the levels of SPLs can mitigate α-Syn accumulation and inhibit AD progression. Meanwhile, loss of SPLs may inhibit the expression of APOE4 and confer protection against AD, while the loss of APOE4 expression also disrupts SPLs homeostasis. Moreover, the heightened activation of sphingomyelinase promotes the ferroptosis signaling pathway, leading to exacerbated AD symptoms. Ferroptosis plays a vital role in the pathological progression of AD by influencing Aβ, tau, APOE, and α-Syn. Conversely, the development of AD also exacerbates the manifestation of ferroptosis and SPLs. We are compiling the emerging techniques (Derivatization and IM-MS) of sphingolipidomics, to overcome the challenges of AD diagnosis and treatment. In this review, we examined the intricate neuro-mechanistic interactions between SPLs and Aβ, tau, α-Syn, APOE, and ferroptosis, mediating the onset of AD. Furthermore, our findings highlight the potential of targeting SPLs as underexplored avenue for devising innovative therapeutic strategies against AD.

Diterpenoids from marine-derived organisms represent a prolific source of secondary metabolites, characterized by their exceptionally promising chemical structures and pronounced pharmacological properties. In recent years, marine diterpenoids have garnered considerable attention and are regarded as a prominent area of scientific research. As a vital class of metabolites, diterpenoids show diverse biological activities, encompassing antibacterial, antifungal, antiviral, anti-inflammatory, inhibitory, and cytotoxic activities, among others. With the rapid advancement of equipment and identified technology, there has been a tremendous surge in the discovery rate of novel diterpenoid skeletons and bioactivities derived from marine fungi over the past decade. The present review compiles the reported diterpenoids from marine fungal sources mainly generated from January 2000 to December 2024. In this paper, 515 diterpenoids from marine organisms are summarized. Among them, a total of 281 structures from various fungal species are included, comprising 55 from sediment, 39 from marine animals (predominantly invertebrates, including 17 from coral and 22 from sponges), and 53 from marine plants (including 34 from algae and 19 from mangrove). Diverse biological activities are exhibited in 244 compounds, and among these, 112 compounds showed great anti-tumor activity (45.90%) and 110 metabolites showed remarkable cytotoxicity (45.08%). Furthermore, these compounds displayed a range of diverse bioactivities, including potent anti-oxidant activity (2.87%), promising anti-inflammatory activity (1.64%), great anti-bacterial activity (1.64%), notable anti-thrombotic activity (1.23%), etc. Moreover, the diterpenoids’ structural characterization and biological activities are additionally elaborated upon. The present critical summary provides a comprehensive overview of the reported knowledge regarding diterpenoids derived from marine fungi, invertebrates, and aquatic plants. The systematic review presented herein offers medical researchers an extensive range of promising lead compounds for the development of marine drugs, thereby furnishing novel and valuable pharmaceutical agents.