Shifting risk profiles in the systemic-to-focal transition of brucellosis: a multicenter analysis of spondyloarthritis development.

Aging constitutes a key contributor to cognitive decline in neurodegenerative conditions, such as various dementias (Liu et al. ). Despite extensive studies on age-related cognitive decline have been conducted over recent decades, the underlying molecular mechanisms remain poorly understood, and effective treatment options continue to be limited (Liu et al. ). Tau hyperphosphorylation is the neuropathological hallmarks of neurodegenerative disorders, including Alzheimer’s disease (AD) (; Liu et al. ). This pathogenic form of tau has been shown to disrupt microtubule stability and axonal transport, ultimately causing neuronal death, and is strongly correlated with cognitive impairment (Alonso et al. ; Huber et al. ). Therefore, delineating the regulatory mechanisms controlling tau hyperphosphorylation represents a promising strategic avenue for developing new treatments for age-related cognitive decline in neurodegenerative diseases. Circular RNAs (circRNAs) belong to a distinct category of endogenous RNAs featured by a covalently closed loop configuration, devoid of a 5’ cap as well as a 3’ poly(A) tail. (Kristensen et al. ). This unique circular conformation makes them more stable than linear RNAs (Kristensen et al. ). CircRNAs were originally regarded as nonfunctional byproducts of aberrant splicing until their capacity to act as microRNA (miRNA) sponges was uncovered (Pisignano et al. ). In recent years, circRNAs have attracted growing attention because of their newly recognized functions in various human disorders, such as cancer, cardiovascular disorders, diabetes, and neurological diseases (Mei and Chen ; Wang et al. ; Yuan et al. ; Zhao et al. ). Notably, circRNAs are enriched in the mammalian brain and accumulate with advancing age (Gruner et al. ; Weigelt et al. ), suggesting their potential involvement in age-related neurodegenerative disorders (Wu et al. ). Indeed, several reports have indicated that circRNAs are differentially expressed in brain tissues derived from the senescence-accelerated mouse prone 8 (SAMP8) strain, and involved with the pathways associated with neurodegenerative disorders, including AD (Huang et al. ; Zhang et al. ). Nevertheless, the role of circRNAs in neurodegenerative diseases remains largely unknown. SAMP8, a naturally occurring mouse strain exhibits a phenotype of accelerated senescence and recapitulates key aspects of age-related neurodegenerative alterations associated with age-related dementia, including age-related cognitive deficits and neuropathological characteristics, such as Aβ deposition, tau hyperphosphorylation, synaptic deficit and neuronal loss, making them an appropriate model for investigating age-related neurodegenerative diseases (Grinan-Ferre et al. ; Jiao et al. ; Pacesova et al. ).