Alzheimer’s disease (AD), an elderly neurodegenerative disorder with a high incidence and progressive memory decline, is one of the most expensive, lethal, and burdening diseases. To date, the pathogenesis of AD has not been fully illustrated. Emerging studies have revealed that cellular senescence and abnormal glucose metabolism in the brain are the early hallmarks of AD. Moreover, cellular senescence and glucose metabolism disturbance in the brain of AD patients may precede amyloid-β deposition or Tau protein phosphorylation. Thus, metabolic reprogramming targeting senescent microglia and astrocytes may be a novel strategy for AD intervention and treatment. Here, we recapitulate the relationships between neural cell senescence and abnormal glucose metabolism (e.g., insulin signaling, glucose and lactate metabolism) in AD. We then discuss the potential perspective of metabolic reprogramming towards an AD intervention, providing a theoretical basis for the further exploration of the pathogenesis of and therapeutic approach toward AD.

Neurodegenerative diseases are common, incurable neurological disorders with high prevalence, and lead to memory, movement, language, and intelligence impairments, threatening the lives and health of patients worldwide. The blood–brain barrier (BBB), a physiological barrier between the central nervous system and peripheral blood circulation, plays an important role in maintaining the homeostasis of the intracerebral environment by strictly regulating the transport of substances between the blood and brain. Therefore, it is difficult for therapeutic drugs to penetrate the BBB and reach the brain, and this affects their efficacy. Nanoparticles (NPs) can be used as drug transport carriers and are also known as nanoparticle-based drug delivery systems (NDDSs). These systems not only increase the stability of drugs but also facilitate the crossing of drugs through the BBB and improve their efficacy. In this article, we provided an overview of the types and administration routes of NPs, highlighted the preclinical and clinical studies of NDDSs in neurodegenerative diseases, and summarized the combined therapeutic strategies in the management of neurodegenerative diseases. Finally, the prospects and challenges of NDDSs in recent basic and clinical research were also discussed. Above all, NDDSs provide an inspiring therapeutic strategy for the treatment of neurodegenerative diseases.

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