Osteoporosis is recognized as a skeletal disorder characterized by diminished bone tissue quality and density. Regular physical exercise is widely acknowledged to preserve and enhance bone health, but the detailed molecular mechanisms involved remain unclear. Irisin, a factor derived from muscle during exercise, influences bone and muscle. Since its discovery in 2012, irisin has been found to promote bone growth and reduce bone resorption, establishing a tangible link between muscle exertion and bone health. Consequently, the mechanism by which irisin prevents osteoporosis have attracted significant scientific interest. This study aims to elucidate the multifaceted relationship between exercise, irisin, and bone health. Focusing on irisin, a muscle-derived factor released during exercise, we seek to understand its role in promoting bone growth and inhibiting resorption. Through a review of current research article on irisin in osteoporosis, Our review provides a deep dive into existing research on influence of irisin in osteoporosis, exploring its interaction with pivotal signaling pathways and its impact on various cell death mechanisms and inflammation. We aim to uncover the molecular underpinnings of how irisin, secreted during exercise, can serve as a therapeutic strategy for osteoporosis. Irisin, secreted during exercise, plays a vital role in bridging muscle function to bone health. It not only promotes bone growth but also inhibits bone resorption. Specifically, Irisin fosters osteoblast proliferation, differentiation, and mineralization predominantly through the ERK, p38, and AMPK signaling pathways. Concurrently, it regulates osteoclast differentiation and maturation via the JNK, Wnt/β-catenin and RANKL/RANK/OPG signaling pathways. This review further delves into the profound significance of irisin in osteoporosis and its involvement in diverse cellular death mechanisms, including apoptosis, autophagy, ferroptosis, and pyroptosis.

Central nervous system (CNS) injury causes severe organ damage due to both damage resulting from the injury and subsequent cell death. However, there are currently no effective treatments for countering the irreversible loss of cell function. Parthanatos is a poly (ADP-ribose) polymerase 1 (PARP-1)-dependent form of programmed cell death that is partly responsible for neural cell death. Consequently, the mechanism by which parthanatos promotes CNS injury has attracted significant scientific interest. Our review aims to summarize the potential role of parthanatos in CNS injury and its molecular and pathophysiological mechanisms. Understanding the role of parthanatos and related molecules in CNS injury is crucial for developing effective treatment strategies and identifying important directions for future in-depth research. Parthanatos (from Thanatos, the personification of death according to Greek mythology) is a type of programmed cell death that is initiated by the overactivation of PARP-1. This process triggers a cascade of reactions, including the accumulation of poly(ADP-ribose) (PAR), the nuclear translocation of apoptosis-inducing factor (AIF) after its release from mitochondria, and subsequent massive DNA fragmentation caused by migration inhibitory factor (MIF) forming a complex with AIF. Secondary molecular mechanisms, such as excitotoxicity and oxidative stress-induced overactivation of PARP-1, significantly exacerbate neuronal damage following initial mechanical injury to the CNS. Furthermore, parthanatos is not only associated with neuronal damage but also interacts with various other types of cell death. This review focuses on the latest research concerning the parthanatos cell death pathway, particularly considering its regulatory mechanisms and functions in CNS damage. We highlight the associations between parthanatos and different cell types involved in CNS damage and discuss potential therapeutic agents targeting the parthanatos pathway.

Neurodegeneration, characterized by the progressive deterioration in neuronal structure or function, presents an elusive mechanism. The use of single-cell RNA sequencing (scRNA-seq) technology in the clinic is becoming increasingly prevalent in recent decades. This technology offers unparalleled cell-level insights into neurodegenerative diseases, establishing itself as a potent tool for elucidating these diseases underlying mechanisms. Here, we made a deep investigation for scRNA-seq research in neurodegenerative diseases using bibliometric analysis from 2009 to 2022. We observed a robust upward trajectory in the number of publications on this subject. The United States stood out as the principal contributor to this expanding field. Specifically, the University of California System exhibited notable research prowess in this field. Alzheimer disease and Parkinson disease were the diseases most frequently investigated. Key research hotspots include the creation of a molecular brain atlas and identification of vulnerable neuronal subpopulations and potential therapeutic targets at the transcriptomic level.

Spinal cord injury (SCI) is a severe central nervous system disorder for which effective therapeutic interventions remain limited. Accumulating evidence indicates that ferroptosis is a key contributor to secondary neuronal damage following SCI, yet its upstream regulators—particularly those involving post-translational modifications such as ubiquitination—remain incompletely understood. This study aimed to determine whether the E3 ubiquitin ligase TRIM59 modulates neuronal ferroptosis and functional recovery after SCI, and to elucidate its molecular substrate and underlying mechanism of action. TRIM59 expression was modulated using lentiviral vectors in cultured neurons and adeno-associated virus serotype 9 (AAV9) in mice. Functional recovery was assessed through the BMS, inclined plane test, footprint analysis, and motor evoked potentials. Ferroptosis was evaluated via biochemical assays, BODIPY C11 staining, ROS detection, TEM, and ferroptosis markers. Molecular interactions were analyzed by co-immunoprecipitation (Co-IP), ubiquitination assays, and cycloheximide (CHX) chase experiment. TRIM59 expression was significantly downregulated during Erastin-induced ferroptosis in neurons and in spinal cord tissue during the acute phase (days 1–3) after SCI. Downregulation of TRIM59 exacerbated the hallmark features of ferroptosis and impaired motor recovery, whereas TRIM59 overexpression attenuated ferroptosis and promoted neurological restoration. Mechanistically, TRIM59 directly bound to ANXA2 and mediated its K48-linked polyubiquitination and subsequent proteasomal degradation. The neuroprotective effect of TRIM59 was abolished by a catalytically inactive C30A mutant or by ANXA2 overexpression, whereas ANXA2 knockdown rescued the ferroptosis and functional deficits induced by TRIM59 deficiency. This study identifies a novel TRIM59–ANXA2 regulatory axis that critically governs neuronal ferroptosis and functional recovery after SCI. TRIM59 functions as an endogenous suppressor of ferroptosis by targeting ANXA2 for K48-linked ubiquitin–proteasome–mediated degradation. These findings not only elucidate a key post-translational mechanism in SCI pathophysiology but also position TRIM59 as a promising therapeutic target for neuroprotection and functional restoration following SCI. Targeting the TRIM59–ANXA2 pathway offers a promising therapeutic strategy to inhibit ferroptosis and promote neuroprotection and functional recovery after SCI. Enhancing TRIM59 activity or disrupting ANXA2 stability could pave the way for novel treatments in clinical neurotrauma.