Exosome-encapsulated microRNAs as promising biomarkers for Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that locks into long clinical latency and low curative ratio. Therefore, early diagnosis before the clinical phase is quite essential and may be effective for therapeutic prevention. Peripheral blood or cerebrospinal fluid biomarkers symbolizing functional neuronal impairment are gradually applied to diagnose AD in research studies. Exosomes have generated immense interest in the diagnosis field of neurodegenerative disorders after confirmation of their roles as mediators, delivering important proteins and microRNAs (miRNAs) in intercellular communication. Compelling research results reveal that miRNAs released from exosomes modulate expression and function of amyloid precursor proteins and tau proteins. These findings open up possibility that dysfunctional exosomal miRNAs may influence AD progression. In this review, we summarized the existing knowledge of exosomal miRNAs and their involvement in AD, emphasizing their potential to serve as diagnostic biomarkers during the preclinical phase of AD.

Potential Roles of Exosomal MicroRNAs as Diagnostic Biomarkers and Therapeutic Application in Alzheimer's Disease.

Exosomes are bilipid layer-enclosed vesicles derived from endosomes and are released from neural cells. They contain a diversity of proteins, mRNAs, and microRNAs (miRNAs) that are delivered to neighboring cells and/or are transported to distant sites. miRNAs released from exosomes appear to be associated with multiple neurodegenerative conditions linking to Alzheimer's disease (AD) which is marked by hyperphosphorylated tau proteins and accumulation of Aß plaques. Exciting findings reveal that miRNAs released from exosomes modulate the expression and function of amyloid precursor proteins (APP) and tau proteins. These open up the possibility that dysfunctional exosomal miRNAs may influence AD progression. In addition, it has been confirmed that the interaction between miRNAs released by exosomes and Toll-like receptors (TLR) initiates inflammation. In exosome support-deprived neurons, exosomal miRNAs may regulate neuroplasticity to relieve neurological damage. In this review, we summarize the literature on the function of exosomal miRNAs in AD pathology, the potential of these miRNAs as diagnostic biomarkers in AD, and the use of exosomes in the delivery of miRNAs which may lead to major advances in the field of macromolecular drug delivery.

Aquaporin 4 in Astrocytes is a Target for Therapy in Alzheimer's Disease.

Current experimental evidence points to the conclusion that aquaporin 4 (AQP4), which is an important water-channel membrane protein found in the brain, could play major roles in various brain conditions pathologically including pathogenesis of Alzheimer's disease (AD). In this paper, we review how AQP4 and altered astrocyte functions interact in AD, and provide experimental evidence highlighting the importance of this topic for the future investigations. The interactions of AQP4 are as follows: (i) AQP4 could influence astrocytic calcium signaling and potassium homeostasis. (ii) AQP4 is linked with the removal of interstitial ß-amyloid and glutamate transmission. (iii) Furthermore, AQP4 modulates the reactive astrogliosis and neuroinflammation mechanisms. (iv) To add to this, AQP4 could participate in the AD pathogenesis through affecting neurotrophic factor production. It is therefore possible to identify certain functional molecules that regulate astrocyte make-up and functions. However, making crucial efforts to develop specific agents or drugs that target AQP4 function and test their therapeutic efficiency will be a breakthrough for addressing AD in that AQP4 controls the various physiological as well as pathophysiological features of astrocytes.

Brain-derived neurotrophic factor: a mediator of inflammation-associated neurogenesis in Alzheimer's disease.

In early- or late-onset Alzheimer's disease (AD), inflammation, which is triggered by pathologic conditions, influences the progression of neurodegeneration. Brain-derived neurotrophic factor (BDNF) has emerged as a crucial mediator of neurogenesis, because it exhibits a remarkable activity-dependent regulation of expression, which suggests that it may link inflammation to neurogenesis. Emerging evidence suggests that acute and chronic inflammation in AD differentially modulates neurotrophin functions, which are related to the roles of inflammation in neuroprotection and neurodegeneration. Recent studies also indicate novel mechanisms of BDNF-mediated neuroprotection, including the modulation of autophagy. Numerous research studies have demonstrated reverse parallel alterations between proinflammatory cytokines and BDNF during neurodegeneration; thus, we hypothesize that one mechanism that underlies the negative impact of chronic inflammation on neurogenesis is the reduction of BDNF production and function by proinflammatory cytokines.

The Neuroprotective Effect of the Association of Aquaporin-4/Glutamate Transporter-1 against Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by memory loss and cognitive dysfunction. Aquaporin-4 (AQP4), which is primarily expressed in astrocytes, is the major water channel expressed in the central nervous system (CNS). This protein plays an important role in water and ion homeostasis in the normal brain and in various brain pathological conditions. Emerging evidence suggests that AQP4 deficiency impairs learning and memory and that this may be related to the expression of glutamate transporter-1 (GLT-1). Moreover, the colocalization of AQP4 and GLT-1 has long been studied in brain tissue; however, far less is known about the potential influence that the AQP4/GLT-1 complex may have on AD. Research on the functional interaction of AQP4 and GLT-1 has been demonstrated to be of great significance in the study of AD. Here, we review the interaction of AQP4 and GLT-1 in astrocytes, which might play a pivotal role in the regulation of distinct cellular responses that involve neuroprotection against AD. The association of AQP4 and GLT-1 could greatly supplement previous research regarding neuroprotection against AD.