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Neurodegeneration

Neurodegeneration refers to the progressive loss of neuron structure or function, which may eventually lead to cell death. Many neurodegenerative diseases, such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease and prion disease, are the results of neurodegenerative processes. Neurodegeneration can be found in many different levels of neuronal circuits in the brain, from molecules to systems. Since there is no known method to reverse the progressive degeneration of neurons, these diseases are considered incurable. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assembly (such as protein diseases) and induction of cell death. These similarities indicate that progress in the treatment of one neurodegenerative disease may also improve other diseases. This collection of entries aims to collect various medical research results related to neurodegeneration. We invite researchers to share their new results and ideas related to neurodegeneration.

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Topic review
Updated time: 30 Jun 2021
Submitted by: Alberto Ouro
Definition: Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson's disease.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 10 May 2021
Submitted by: Adolfo Toledano
Definition: Classical scrapie is a naturally transmissible spongiform neurodegenerative disease that originally affected sheep, goats and mouflons and that has been observed for several centuries. It is a “strange” disease that cannot be classified as a classical bacterial or viral infectious disease and does not follow the pathogenic patterns identified by infectious or neurodegenerative disease research.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 02 Jul 2021
Submitted by: Marco Diociaiuti
Definition: It has been proposed that a “common core” of pathologic pathways exists for the large family of amyloid-associated neurodegenerations, including Alzheimer’s, Parkinson’s, type II diabetes and Creutzfeldt–Jacob’s Disease. Aggregates of the involved proteins, independently from their primary sequence, induced neuron membrane permeabilization able to trigger an abnormal Ca2+ influx leading to synaptotoxicity, resulting in reduced expression of synaptic proteins and impaired synaptic transmission. Emerging evidence is now focusing on low-molecular-weight prefibrillar oligomers (PFOs), which mimic bacterial pore-forming toxins that form well-ordered oligomeric membrane-spanning pores. At the same time, the neuron membrane composition and its chemical microenvironment seem to play a pivotal role. However, up to now the existence of a specific “common structure” of the toxic aggregate, and a “common mechanism” by which it induces neuronal damage, synaptotoxicity and impaired synaptic transmission, is still an open hypothesis. In this review, we gathered information concerning this hypothesis, focusing on the proteins linked to several amyloid diseases. We noted commonalities in their structure and membrane activity, and their ability to induce Ca2+ influx, neurotoxicity, synaptotoxicity and impaired synaptic transmission.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 15 Mar 2021
Submitted by: Maurits Vissers
Definition: The clinical failure rate for disease-modifying treatments (DMTs) that slow or stop disease progression has been nearly 100% for the major neurodegenerative disorders (NDDs), with many compounds failing in expensive and time-consuming phase 2 and 3 trials for lack of efficacy. However, as our understanding of NDDs is improving, there is a rise in potentially disease-modifying treatments being brought to the clinic. Further increasing the rational use of mechanistic biomarkers in early phase trials for these (targeted) therapies can increase R&D productivity with a quick win/fast fail approach in an area that has seen a nearly 100% failure rate to date.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 05 Mar 2021
Submitted by: Kimitoshi Nakamura
Definition: Dissociated optic nerve fiber layer (DONFL) appearance is characterized by dimpling of the fundus when observed after vitrectomy with the internal limiting membrane (ILM) peeling in macular diseases. However, the cause of DONFL remains largely unknown. Optical coherence tomography (OCT) findings have indicated that the nerve fiber layer (NFL) and ganglion cells are likely to have been damaged in patients with DONFL appearance. Since DONFL appearance occurs at a certain postoperative period, it is unlikely to be retinal damage directly caused by ILM peeling because apoptosis occurs at a certain period after tissue damage and/or injury. However, it may be due to ILM peeling-induced apoptosis in the retinal tissue. Anoikis is a type of apoptosis that occurs in anchorage-dependent cells upon detachment of those cells from the surrounding extracellular matrix (i.e., the loss of cell anchorage). The anoikis-related proteins βA3/A1 crystallin and E-cadherin are reportedly expressed in retinal ganglion cells.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 17 Jun 2021
Submitted by: Mateusz Jurga
Definition: As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 18 Jun 2021
Submitted by: KULBHUSHAN SHARMA
Definition: Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). A possible causative role for DNA damage and DNA repair in the pathogenesis of common, late-onset NDDs is less well established, although DDR defects are emerging as possible culprits in diseases like AD, PD, and ALS. Whether targeting DNA repair or the DDR may be developed into therapeutic options against NDDs remains to be clarified.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 17 Aug 2021
Submitted by: Shin-Da Lee
Definition: Treadmill training attenuated complex I deficits, cytochrome c release, ATP depletion, and complexes II–V abnormalities in Parkinson’s disease. Studies analyzed the neural mitochondrial quality-control, reporting that treadmill exercise improved mitochondrial biogenesis, mitochondrial fusion, and mitophagy in Parkinson’s disease. The hypothesis that treadmill training could attenuate both neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson’s disease, suggesting that treadmill training might slow down the progression of Parkinson’s disease.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 20 May 2021
Submitted by: Dong-Kug Choi
Definition: Neurodegenerative diseases are a large group of neurological disorders with diverse etiological and pathological phenomena. However, current therapeutics rely mostly on symptomatic relief while failing to target the underlying disease pathobiology. G-protein-coupled receptors (GPCRs) are one of the most frequently targeted receptors for developing novel therapeutics for central nervous system (CNS) disorders. Many currently available antipsychotic therapeutics also act as either antagonists or agonists of different GPCRs. Therefore, GPCR-based drug development is spreading widely to regulate neurodegeneration and associated cognitive deficits through the modulation of canonical and noncanonical signals.
Entry Collection : Neurodegeneration
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Topic review
Updated time: 13 May 2021
Submitted by: Koji Aoyama
Definition: Glutathione (GSH) is the most abundant non-protein thiol, and plays crucial roles in the antioxidant defense system and the maintenance of redox homeostasis in neurons.
Entry Collection : Neurodegeneration
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