The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission—An Up-to-Date Review

Abstract

Depression is a serious neuropsychiatric disease affecting an increasing number of people worldwide. Cognitive deficits (including inattention, poor memory, and decision-making difficulties) are common in the clinical picture of depression. Cognitive impairment has been hypothesized to be one of the most important components of major depressive disorder (MDD; referred to as clinical depression), although typical cognitive symptoms are less frequent in people with depression than in people with schizophrenia or bipolar disorder (BD; sometimes referred to as manic-depressive disorder). The importance of α-Klotho in the aging process has been well-documented. Growing evidence points to the role of α-Klotho in regulating other biological functions, including responses to oxidative stress and the modulation of synaptic plasticity. It has been proven that a Klotho deficit may contribute to the development of various nervous system pathologies, such as behavioral disorders or neurodegeneration. Given the growing evidence of the role of α-Klotho in depression and cognitive impairment, it is assumed that this protein may be a molecular link between them. Here, we provide a research review of the role of α-Klotho in depression and cognitive impairment. Furthermore, we propose potential mechanisms (related to oxidative stress and glutamatergic transmission) that may be important in α-Klotho-mediated regulation of mental and cognitive function.

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders

“…A study suggests that plasma exosomal concentration of PrP c may serve as a biomarker of cognitive decline in this disorder [ 13 ]. Cognitive impairments are prevalent and debilitating symptoms in affective disorders [ 138 ]. Further studies should evaluate whether serum PrP c concentration may be used as a biomarker of the severity of those symptoms among patients diagnosed with mood disorders.…”