Neuroscience
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the 2019 coronavirus disease (COVID-19), has affected more than 20 million people in Brazil and caused a global health emergency. This virus has the potential to affect various parts of the body and compromise metabolic functions. The virus-mediated neural inflammation of the nervous system is due to a storm of cytokines and oxidative stress, which are the clinical features of Alzheimer's disease (AD). ⋯ The cholinergic system, through neurons and the neurotransmitter acetylcholine (ACh), modulates various physiological pathways, such as the response to stress, sleep and wakefulness, sensory information, and the cognitive system. Patients with AD have low concentrations of ACh; hence, therapeutic methods are aimed at adjusting the ACh titers available to the body for maintaining functionality. Herein, we focused on acetylcholinesterase inhibitors, responsible for the degradation of ACh in the synaptic cleft, and muscarinic and nicotinic receptor agonists of the cholinergic system owing to the therapeutic potential of the cholinergic anti-inflammatory pathway in AD associated with SARS-CoV-2 infection.
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Nuclear TAR DNA-binding protein 43 (TDP-43) mitigates cellular function, but the dynamic nucleus-cytoplasm shuttling of TDP-43 is disrupted in diseases, such as Amyotrophic Lateral Sclerosis (ALS). The polymorphic nature of the TDP-43 structures in vitro and in vivo is a result of environmental factors leading to the protein pathogenesis. Once the triggers which mitigate TDP-43 biochemistry are identified, new therapies can be developed. This review aims to illustrate recent discoveries in the diversity of TDP-43 structures (amyloidogenic and non-amyloidogenic) and highlight the triggers which result in their formation.
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Alzheimer's disease (AD) is a disorder of the central nervous system that is typically marked by progressive cognitive impairment and memory loss. Amyloid β plaque deposition and neurofibrillary tangles with hyperphosphorylated tau are the two hallmark pathologies of AD. In mammalian cells, autophagy clears aberrant protein aggregates, thus maintaining proteostasis as well as neuronal health. ⋯ On the other hand, defective autophagy has been found to induce the production of the neuroprotective factor fibroblast growth factor 21 (FGF21), although the underlying mechanism is unclear. In this review, we highlight the significance of aberrant autophagy in the pathogenesis of AD, discuss the possible mechanisms by which defective autophagy induces FGF21 production, and analyze the potential of FGF21 in the treatment of AD. The findings provide some insights into the potential role of FGF21 and autophagy in the pathogenesis of AD.
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Parkinson's disease (PD) is the world's second primary neurodegenerative disease, and the diagnosis and treatment of PD have become mainstream research. Over the past decades, several studies have identified potential biomarkers for diagnosing PD. Among them, extracellular vesicles (EVs) can carry specific biomarkers reflecting the physiological and pathological state of the body. ⋯ In this review, we summarized previous studies on PD diagnosis biomarkers in peripheral blood EVs and evaluated their diagnostic value. Some EV surface markers were also described, which can extract EVs from specific cell origins. In addition, the combination of several biomarkers demonstrated good diagnostic performance in PD diagnosis compared with a single biomarker, suggesting the focus of future research.
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Review
Relevance of biochemical deep phenotyping for a personalised approach to Parkinson's disease.
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder characterised by the progressive loss of dopaminergic neurons in the nigrostriatal tract. The identification of disease-modifying therapies is the Holy Grail of PD research, but to date no drug has been approved as such a therapy. A possible reason is the remarkable phenotypic heterogeneity of PD patients, which can generate confusion in the interpretation of results or even mask the efficacy of a therapeutic intervention. ⋯ The analyte most studied is α-synuclein, while other studies have focused on neurofilament light chain, lysosomal proteins, inflammasome-related proteins, LRRK2 and the urinary proteome. At present, stratification of PD patients, while promising, is still a nascent approach. Deep phenotyping of patients will allow clinical researchers to identify homogeneous subgroups for the investigation of tailored disease-modifying therapies, enhancing the chances of therapeutic success.