The key roles of organelles and ferroptosis in Alzheimerʼs disease

Abstract

Alzheimerʼs disease (AD), an age-related neurodegenerative disease, is a striking global health problem. Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation products and the accumulation of lethal reactive oxygen species. Strict regulation of iron metabolism is essential to ensure neuronal homeostasis. Excess and deficiency of iron are both associated with neurodegeneration.Studies have shown that oxidative stress caused by cerebral iron metabolism disorders in the body is involved in the process of AD, ferroptosis may play an important role in the pathogenesis of AD, and regulating ferroptosis is expected to be a new direction for the treatment of AD. Various organelles are closely related to ferroptosis: mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome are involved in the regulation of ferroptosis from the aspects of iron metabolism and redox imbalance. In this review, the relationship between AD and the dysfunction of organelles (including mitochondria, endoplasmic reticulum, lysosome, and Golgi apparatus) and the role of organelles in ferroptosis of AD were reviewed to provide insights for understanding the relationship between organelles and ferroptosis in AD and the treatment of AD.

Jingfang granules protects against intracerebral hemorrhage by inhibiting neuroinflammation and protecting blood-brain barrier damage

“…PI3K/AKT is a key regulator of cell behaviors such as apoptosis, proliferation and differentiation [49]. In particular, it plays a neuroprotective role in diseases of the central nervous system, such as Alzheimer's disease (AD) [50,51], Parkinson disease (PD) [52,53], IS [54,55], and ICH [56][57][58]. Studies of Bao Yu [59] and Han Cai Ping [60] have shown that PI3K and P-AKT protein expression will show an increase in 6 h after the mouse ICH is made.…”

Plasma metabolomic characterization of premature ovarian insufficiency

“…In contrast, cystine deprivation was implicated in ferroptosis, a novel iron-dependent form of regulated cell death that is driven by excessive oxidative damage to lipids [53]. Although the relationship between ferroptosis and POI has not been clarified, the accumulated evidence indicates that ferroptosis contributes to the major complications of POI, including cardiovascular disease [54], neurodegenerative disease [55], and osteoporosis [56]. According to a recent report published in Science, cystine also acts as a key regulator in diet-regulated growth suppression programs, such as autophagy [57], which is critical for ovarian function and participates in the pathogenesis of POI [58].…”

Lipid metabolism transcriptomics of murine microglia in Alzheimer’s disease and neuroinflammation

“…The Golgi apparatus is essential for the synthesis and modification of proteins and lipids, and Golgi fragmentation has been observed in AD 52 . Golgi fragmentation is suggested to promote neuronal ion channel damage and the accumulation of tau and Aβ 53 . Specialized regions of plasma membranes, such as caveolae, modulate reactive oxygen species (ROS) producing systems 54 .…”