Summary

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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Entries
Topic Review
DNA-Repair Pathways: Links to Neurodegeneration
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.
  • 731
  • 18 Jun 2021
Topic Review
DNA Homeostasis and Senescence
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.  
  • 628
  • 17 Jun 2021
Topic Review
Polyphenols and Neuroprotection
Polyphenols are naturally occurring micronutrients that are present in many food sources. Besides being potent antioxidants, these molecules may also possess anti-inflammatory properties. Many studies have highlighted their potential role in the prevention and treatment of various pathological conditions connected to oxidative stress and inflammation (e.g., cancer, and cardiovascular and neurodegenerative disorders). Neurodegenerative diseases are globally one of the main causes of death and represent an enormous burden in terms of human suffering, social distress, and economic costs. Recent data expanded on the initial antioxidant-based mechanism of polyphenols’ action by showing that they are also able to modulate several cell-signaling pathways and mediators. The proposed benefits of polyphenols, either as protective/prophylactic substances or as therapeutic molecules, may be achieved by the consumption of a natural polyphenol-enriched diet, by their use as food supplements, or with formulations as pharmaceutical drugs/nutraceuticals.
  • 589
  • 15 Jun 2021
Topic Review
G-Protein-Coupled Receptors in CNS
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.
  • 913
  • 20 May 2021
Topic Review
Ubisol-Q10 for Neurodegenerative Disease Treatment
It is well established and accepted that excessive oxidative stress is a key contributor to neurodegenerative diseases, driving interest in the development and application of redox therapies including the use of coenzyme-Q10 (CoQ10). However, in several human clinical trials, CoQ10 has failed to show efficacy, possibly due to poor tissue penetration and inability to deliver it parenterally. Ubisol-Q10 is a nanomicellar, water-dispersible formulation of CoQ10 that was created by combining CoQ10 with an amphiphilic and self-emulsifying molecule of polyoxyethanyl α-tocopheryl sebacate (PTS). This stable formulation is suitable for parenteral delivery and when tested at micromolar concentrations (well within FDA guidelines), it showed unprecedented neuroprotection, both in cellular models and animal models of chronic progressive neurodegeneration of both Parkinson’s and Alzheimer’s type. Systemic application of Ubisol-Q10 in drinking water stopped further progression of ongoing neurodegeneration as long as Ubisol-Q10 was provided. Mechanistically, this treatment with Ubisol-Q10 mobilized astroglia response in the CNS, quenched reactive oxygen species, prevented cell senescence, activated autophagy, reduced inflammation, and stabilized mitochondria. Importantly, these biochemical outcomes are accompanied by a significant improvement in behavioral deficits typically observed in animals with Parkinson’s and Alzheimer’s disease. Thus, Ubisol-Q10 is a promising candidate for developing a disease-modifying therapeutic intervention for neurodegenerative diseases that can be easily administered as drinking tonic.
  • 639
  • 20 May 2021
Topic Review
Symptomatic Treatments for Chronic Neurodegeneration
Symptomatic treatments are available for Parkinson’s disease and Alzheimer’s disease. An unmet need is cure or disease modification. This review discusses possible reasons for negative clinical study outcomes on disease modification following promising positive findings from experimental research. It scrutinizes current research paradigms for disease modification with antibodies against pathological protein enrichment, such as α-synuclein, amyloid or tau, based on post mortem findings. Instead a more uniform regenerative and reparative therapeutic approach for chronic neurodegenerative disease entities is proposed with stimulation of an endogenously existing repair system, which acts independent of specific disease mechanisms. The repulsive guidance molecule A pathway is involved in the regulation of peripheral and central neuronal restoration. Therapeutic antagonism of repulsive guidance molecule A reverses neurodegeneration according to experimental outcomes in numerous disease models in rodents and monkeys. Antibodies against repulsive guidance molecule A exist. First clinical studies in neurological conditions with an acute onset are under way. Future clinical trials with these antibodies should initially focus on well characterized uniform cohorts of patients. The efficiency of repulsive guidance molecule A antagonism and associated stimulation of neurogenesis should be demonstrated with objective assessment tools to counteract dilution of therapeutic effects by subjectivity and heterogeneity of chronic disease entities. Such a research concept will hopefully enhance clinical test strategies and improve the future therapeutic armamentarium for chronic neurodegeneration
  • 360
  • 20 May 2021
Topic Review
Microglia in Sepsis-Associated Encephalopathy
Multiple organ dysfunction is a hallmark of sepsis pathogenesis, and neurological manifestations are a frequent and underestimated symptom. Sepsis induces an acute brain dysfunction that is not related to direct brain infection and is characterized by clinical and electroencephalographic changes that range from sickness behavior to altered consciousness, varying from confusion to delirium and coma.
  • 445
  • 17 May 2021
Topic Review
Serotonin
Serotonin (5-hydroxytryptamine, 5-HT) plays two important roles in humans—one central and the other peripheral—depending on the location of the 5-HT pools of on either side of the blood-brain barrier. In the central nervous system it acts as a neurotransmitter, controlling such brain functions as autonomic neural activity, stress response, body temperature, sleep, mood and appetite. This role is very important in intensive care, as in critically ill patients multiple serotoninergic agents like opioids, antiemetics and antidepressants are frequently used. High serotonin levels lead to altered mental status, deliria, rigidity and myoclonus, together recognized as serotonin syndrome. In its role as a peripheral hormone, serotonin is unique in controlling the functions of several organs. In the gastrointestinal tract it is important for regulating motor and secretory functions. Apart from intestinal motility, energy metabolism is regulated by both central and peripheral serotonin signaling. It also has fundamental effects on hemostasis, vascular tone, heart rate, respiratory drive, cell growth and immunity. Serotonin regulates almost all immune cells in response to inflammation, following the activation of platelets. 
  • 3.9K
  • 18 May 2021
Topic Review
Glutathione in the Brain
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.
  • 745
  • 13 May 2021
Topic Review
Matrix Metalloproteinases in Neurodegenerative Diseases
Neurodegenerative disorders/diseases (NDs) are a chronic debilitating group of heterogeneous diseases, which include loss of neuronal function and structure, leading to neuronal cell death or progressive degeneration. NDs comprise a highly complex etiology that is mainly associated with abnormal protein accumulation, mutated genes, increased reactive oxygen species (ROS), neuroinflammation, mitochondrial dysfunction, apoptosis, elevated endoplasmic reticulum (ER), calcium overload, excitotoxicity, or neuronal destruction in specific regions of the brain. ND is a wide array of neurological disorders that generally affect central nervous system (CNS) neurons, characterized by progressive neuronal dysfunction in the CNS, resulting in deficit of specific functions of the brain (movement, memory, and cognition). These processes are involved in the pathogenesis and progression of NDs, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson’s disease.
  • 412
  • 12 May 2021
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