Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia

Abstract

Central nervous system parvalbumin-positive interneurons (PV-INs) are crucial and highly vulnerable to various stressors. They also play a significant role in the pathological processes of many neuropsychiatric diseases, especially those associated with cognitive impairment, such as Alzheimer’s disease (AD), vascular dementia (VD), Lewy body dementia, and schizophrenia. Although accumulating evidence suggests that the loss of PV-INs is associated with memory impairment in dementia, the precise molecular mechanisms remain elusive. In this review, we delve into the current evidence regarding the physiological properties of PV-INs and summarize the latest insights into how their loss contributes to cognitive decline in dementia, particularly focusing on AD and VD. Additionally, we discuss the influence of PV-INs on brain development, the variations in their characteristics across different types of dementia, and how their loss affects the etiology and progression of cognitive impairments. Ultimately, our goal is to provide a comprehensive overview of PV-INs and to consider their potential as novel therapeutic targets in dementia treatment.