TFEB dysregulation as a driver of autophagy dysfunction in neurodegenerative disease: Molecular mechanisms, cellular processes, and emerging therapeutic opportunities.

TFEB dysregulation as a driver of autophagy dysfunction in neurodegenerative disease: Molecular mechanisms, cellular processes, and emerging therapeutic opportunities. Neurobiol Dis. 2018 May 28;: Authors: Cortes CJ, La Spada AR Abstract Two decades ago, the recognition of protein misfolding and aggregate accumulation as defining features of neurodegenerative disease set the stage for a thorough examination of how protein quality control is maintained in neurons and in other non-neuronal cells in the central nervous system (CNS). Autophagy, a pathway of cellular self-digestion, has emerged as especially important for CNS proteostasis, and autophagy dysregulation has been documented as a defining feature of neurodegeneration in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Transcription factor EB (TFEB) is one of the main transcriptional regulators of autophagy, as it promotes the expression of genes required for autophagosome formation, lysosome biogenesis, and lysosome function, and it is highly expressed in CNS. Over the last 7 years, TFEB has received considerable attention and TFEB dysfunction has been implicated in the pathogenesis of numerous neurodegenerative disorders. In this review, we delineate the current understanding of how TFEB dysregulation is involved in neurodegeneration, highlighting work done on AD, PD, HD, X-linked spinal &bulbar muscular atrophy, and amyotrophic lateral sclerosis. Because T...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research

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Abstract The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At the same time, the BBB regulates transport of molecules into and out of the central nervous system (CNS), which maintains tightly controlled chemical composition of the neuronal milieu that is required for proper neuronal functioning. In this review, we first examine molecular and cellular mechanisms underlying the establishment of the BBB. Then, we focus on BBB transport physiology, endothelial and pericyte transporters, and perivascular and paravascular transport. Next, we discuss ...
Source: Physiological Reviews - Category: Physiology Authors: Tags: Physiol Rev Source Type: research
Conclusion: The network of exosomes and miRNAs that regulates CNS homeostasis is a promising biomarker for the diagnosis and treatment of neurodegenerative diseases. PMID: 30203797 [PubMed - in process]
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
Abstract Spices are not only just herbs used in culinary for improving the taste of dishes. They are also sources of a numerous bioactive compounds significantly beneficial for health. They have been used since ancient times because of their antimicrobial, anti-inflammatory and carminative properties. Several scientific studies have suggested their protective role against chronic diseases. In fact, their active compounds may help in arthritis, neurodegenerative disorders (Alzheimer's, Parkinson, Huntington's disease, amyotrophic lateral sclerosis, etc.), diabetes, sore muscles, gastrointestinal problems and many m...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
uiz J Abstract The endocannabinoid system (ECS) exerts a modulatory effect of important functions such as neurotransmission, glial activation, oxidative stress, or protein homeostasis. Dysregulation of these cellular processes is a common neuropathological hallmark in aging and in neurodegenerative diseases of the central nervous system (CNS). The broad spectrum of actions of cannabinoids allows targeting different aspects of these multifactorial diseases. In this review, we examine the therapeutic potential of the ECS for the treatment of chronic neurodegenerative diseases of the CNS focusing on Alzheimer's disea...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
In this study, we assessed the antioxidant properties of Larrea tridentata, collected specifically from the Chihuahuan desert in the region of El Paso del Norte, TX, USA. LT phytochemicals were obtained from three different extracts (ethanol; ethanol: water (60:40) and water). Then the extracts were evaluated in eight different assays (DPPH, ABTS, superoxide; FRAP activity, nitric oxide, phenolic content, UV visible absorption and cytotoxicity in non-cancerous HS27 cells). The three extracts were not affecting the HS27 cells at concentrations up to 120 µg/mL. Among the three extracts, we found that the mixture of...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
In conclusion, we focus on the various newer molecular mechanisms that are associated with the basic understanding of neuroinflammation in neurodegeneration.
Source: Neurochemistry International - Category: Neuroscience Source Type: research
Abstract Many evidences indicate that oxidative stress plays a significant role in a variety of human disease states, including neurodegenerative diseases. Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing proteins and enzymes, though it could be also toxic. Actually, free iron excess generates oxidative stress, particularly in brain, where anti-oxidative defences are relatively low. Its accumulation in specific regions is associated with pathogenesis in a variety of neurodegenerative diseases (i.e., Parkinson's disease, Alzheimer's disease, Hunt...
Source: Biometals - Category: Biochemistry Authors: Tags: Biometals Source Type: research
Publication date: Available online 7 July 2018Source: Pharmacological ResearchAuthor(s): Samira Shirooie, Seyed Fazel Nabavi, Ahmad R. Dehpour, Tarun Belwal, Solomon Habtemariam, Sandro Argüelles, Antoni Sureda, Maria Daglia, Michał Tomczyk, Eduardo Sobarzo-Sanchez, Suowen Xu, Seyed Mohammad NabaviAbstractNeurodegenerative diseases (NDs) such as Parkinson's (PD), Alzheimer's (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) cause significant world-wide morbidity and mortality. To date, there is no drug of cure for these, mostly age-related diseases, although approaches in delaying the pathology...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: July 2018Source: Neurochemistry International, Volume 117Author(s): Carlo Rodolfo, Silvia Campello, Francesco CecconiAbstractNeurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), are a complex “family” of pathologies, characterised by the progressive loss of neurons and/or neuronal functions, leading to severe physical and cognitive inabilities in affected patients. These syndromes, despite differences in the causative events, the onset, and the progression of the disease, share as common feat...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
Publication date: Available online 7 July 2018Source: Pharmacological ResearchAuthor(s): Samira Shirooie, Seyed Fazel Nabavi, Ahmad R. Dehpour, Tarun Belwal, Solomon Habtemariam, Sandro Argüelles, Antoni Sureda, Maria Daglia, Michał Tomczyk, Eduardo Sobarzo-Sanchez, Suowen Xu, Seyed Mohammad NabaviAbstractNeurodegenerative diseases (NDs) such as Parkinson's (PD), Alzheimer's (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) cause significant world-wide morbidity and mortality. To date, there is no drug of cure for these, mostly age-related diseases, although approaches in delaying the pathology...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
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