• BMB Reports
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• v.49 no.8
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• pp.405-413
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• 2016

Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.239-253
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• 2010

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

• BMB Reports
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• v.50 no.7
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• pp.345-354
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• 2017

Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

• The Korean Journal of Nuclear Medicine
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• v.37 no.1
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• pp.34-42
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• 2003

The dopamine transporter (DAT) is responsible for the re-uptake of dopamine from the synaptic cleft and is located on dopaminergic nerve terminals only. DAT single photon emission computed tomography (SPECT) and positron omission tomography (PET) imaging, therefore, offer the unique opportunity to study via striatal uptake the integrity of presynaptic dopaminergic nerve terminals in vivo. In recent years SPECT and PET using specific ligands binding to DAT have evolved as an useful tool for diagnosing and monitoring progression of neurodegenerative disorders affecting dopaminergic systems. This article briefly reviews the literature dealing with DAT SPECT and PET imaging in parkinsonism and other neurodegenerative disorders.

• Interdisciplinary Bio Central
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• v.2 no.4
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• pp.9.1-9.5
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• 2010

Many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are devastating disorders that affect millions of people worldwide. However, the number of therapeutic options remains severely limited with only symptomatic management therapies available. With the better understanding of the pathogenesis of neurodegenerative diseases, discovery efforts for disease-modifying drugs have increased dramatically in recent years. However, the process of translating basic science discovery into novel therapies is still lagging behind for various reasons. The task of finding new effective drugs targeting central nervous system (CNS) has unique challenges due to blood-brain barrier (BBB). Furthermore, the relatively slow progress of neurodegenerative disorders create another level of difficulty, as clinical trials must be carried out for an extended period of time. This review is intended to provide molecular and cell biologists with working knowledge and resources on CNS drug discovery and development.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.133-143
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• 2012

Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of ${\alpha}$-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

• Molecules and Cells
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• v.38 no.5
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• pp.381-389
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• 2015

Autophagy is a lysosome-dependent intracellular degradation process that allows recycling of cytoplasmic constituents into bioenergetic and biosynthetic materials for maintenance of homeostasis. Since the function of autophagy is particularly important in various stress conditions, perturbation of autophagy can lead to cellular dysfunction and diseases. Accumulation of abnormal protein aggregates, a common cause of neurodegenerative diseases, can be reduced through autophagic degradation. Recent studies have revealed defects in autophagy in most cases of neurodegenerative disorders. Moreover, deregulated excessive autophagy can also cause neurodegeneration. Thus, healthy activation of autophagy is essential for therapeutic approaches in neurodegenerative diseases and many autophagy-regulating compounds are under development for therapeutic purposes. This review describes the overall role of autophagy in neurodegeneration, focusing on various therapeutic strategies for modulating specific stages of autophagy and on the current status of drug development.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.596-604
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• 2021

Different lifestyles have an impact on useful metabolic functions, causing disorders. Different lipids are involved in the metabolic functions that play various vital roles in the body, such as structural components, storage of energy, in signaling, as biomarkers, in energy metabolism, and as hormones. Inter-related disorders are caused when these functions are affected, like diabetes, cancer, infections, and inflammatory and neurodegenerative conditions in humans. During the Covid-19 period, there has been a lot of focus on the effects of metabolic disorders all over the world. Hence, this review collectively reports on research concerning metabolic disorders, mainly cardiovascular and diabetes mellitus. In addition, drug research in lipid metabolism disorders have also been considered. This review explores lipids, metabolism, lipid metabolism disorders, and drugs used for these disorders.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.232.2-232.2
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• 2003

Many neurodegenerative disorders such as stroke, Alzheimer's disease, and Parkinson's disease have been known to be associated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. Therefore, the antioxidants have recently received much attention as therapeutic agent for the treatment of neurodegenerative disease. (omitted)

• BMB Reports
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• v.40 no.1
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• pp.125-129
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• 2007

Neurofilament-L (NF-L) is a major element of the neuronal cytoskeleton and is essential for neuronal survival. Moreover, abnormalities in NF-L result in neurodegenerative disorders. Carnosine and the related endogeneous histidine dipeptides prevent protein modifications such as oxidation and glycation. In the present study, we investigated whether histidine dipeptides, carnosine, homocarnosine, or anserine protect NF-L against oxidative modification during reaction between cytochrome c and $H_2O_2$. Carnosine, homocarnosine and anserine all prevented cytochrome c/$H_2O_2$-mediated NF-L aggregation. In addition, these compounds also effectively inhibited the formation of dityrosine, and this inhibition was found to be associated with the reduced formations of oxidatively modified proteins. Our results suggest that carnosine and histidine dipeptides have antioxidant effects on brain proteins under pathophysiological conditions leading to degenerative damage, such as, those caused by neurodegenerative disorders.