1. The function of sphingolipids in different pathogenesis of Alzheimer's disease: A comprehensive review.
- Author
-
Wang, Xinyi, Li, Huaqiang, Sheng, Yunjie, He, Bingqian, Liu, Zeying, Li, Wanli, Yu, Shujie, Wang, Jiajing, Zhang, Yixin, Chen, Jianyu, Qin, Luping, and Meng, Xiongyu
- Subjects
- *
ALZHEIMER'S disease , *SPHINGOLIPIDS , *CHRONIC traumatic encephalopathy , *TAU proteins , *TECHNOLOGICAL innovations , *BLEPHAROPTOSIS , *MICROTUBULE-associated proteins - Abstract
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. [Display omitted] • The emerging technologies field of sphingolipidomic significantly improved the detectability to achieve more SPL biomarkers. • SPLs can affect AD development by regulating different pathogenesis (Aβ, tau, APOE, and α-Syn) of AD. • Ferroptosis may be a crucial potential pathway by which SPLs regulate AD. • Changes in SPLs might activate ferroptosis pathway consequently the pathogenesis of Aβ, tau, APOE, and α-Syn aggravated AD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF