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
Adenosine Targeting Strategy for Glioblastoma Aggressiveness
Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. 
  • 518
  • 05 Sep 2022
Topic Review
Synaptic Disruption by Soluble Oligomers in Neurodegenerative Diseases
Neurodegenerative diseases are the result of progressive dysfunction of the neuronal activity and subsequent neuronal death. Currently, the most prevalent neurodegenerative diseases are by far Alzheimer’s (AD) and Parkinson’s (PD) disease, affecting millions of people worldwide. Although amyloid plaques and neurofibrillary tangles are the neuropathological hallmarks for AD and Lewy bodies (LB) are the hallmark for PD, current evidence strongly suggests that oligomers seeding the neuropathological hallmarks are more toxic and disease-relevant in both pathologies. The presence of small soluble oligomers is the common bond between AD and PD: amyloid β oligomers (AβOs) and Tau oligomers (TauOs) in AD and α-synuclein oligomers (αSynOs) in PD. Such oligomers appear to be particularly increased during the early pathological stages, targeting synapses at vulnerable brain regions leading to synaptic plasticity disruption, synapse loss, inflammation, excitation to inhibition imbalance and cognitive impairment. Absence of TauOs at synapses in individuals with strong AD disease pathology but preserved cognition suggests that mechanisms of resilience may be dependent on the interactions between soluble oligomers and their synaptic targets.
  • 484
  • 31 Aug 2022
Topic Review
Link of Mitochondrial Quality Control and Parkinson’s Disease
Dysfunctional mitochondrial quality control (MQC) is implicated in the pathogenesis of Parkinson’s disease (PD). The improper selection of mitochondria for mitophagy increases reactive oxygen species (ROS) levels and lowers ATP levels. The downstream effects include oxidative damage, failure to maintain proteostasis and ion gradients, and decreased NAD+ and NADPH levels, resulting in insufficient energy metabolism and neurotransmitter synthesis. A ketosis-based metabolic therapy that increases the levels of (R)-3-hydroxybutyrate (BHB) may reverse the dysfunctional MQC by partially replacing glucose as an energy source, by stimulating mitophagy, and by decreasing inflammation. Fasting can potentially raise cytoplasmic NADPH levels by increasing the mitochondrial export and cytoplasmic metabolism of ketone body-derived citrate that increases flux through isocitrate dehydrogenase 1 (IDH1). NADPH is an essential cofactor for nitric oxide synthase, and the nitric oxide synthesized can diffuse into the mitochondrial matrix and react with electron transport chain-synthesized superoxide to form peroxynitrite. Excessive superoxide and peroxynitrite production can cause the opening of the mitochondrial permeability transition pore (mPTP) to depolarize the mitochondria and activate PINK1-dependent mitophagy. Both fasting and exercise increase ketogenesis and increase the cellular NAD+/NADH ratio, both of which are beneficial for neuronal metabolism.
  • 501
  • 31 Aug 2022
Topic Review
HDL-Mediated Cholesterol Trafficking in the Central Nervous System
Alzheimer’s disease (AD) is characterized by the accumulation of extracellular amyloid beta (Aβ) and abnormally hyperphosphorylated intracellular tau filaments in neurons. Cholesterol metabolism has been extensively implicated in the pathogenesis of AD through biological, epidemiological, and genetic studies, with the APOE gene being the most reproducible genetic risk factor for the development of AD. The apolipoprotein E (ApoE) 4  genotype seems to be a disruptive element in high-density lipoprotein (HDL)-like-mediated cholesterol transport through the brain. 
  • 520
  • 30 Aug 2022
Topic Review
Physiological TDP-43 Structure and Function
TAR-DNA binding protein-43 (TDP-43) is a ubiquitously expressed RNA binding protein with the capacity to bind over 6000 RNA and DNA targets—particularly those involved in RNA, mitochondrial, and lipid metabolism. The specific functions of TDP-43 include mRNA stabilisation, transcription, translation, splicing, axonal transport, apoptosis, microRNA processing, epigenetic modifications, and cryptic exon inclusion/repression. It is without doubt that any alteration to these structural domains and/or normal functions of TDP-43 could cause downstream destabilisation effects of the intended target(s). This entry discusses briefly the structure of the TDP-43 protein, and some of their functional impact in amyotrophic lateral sclerosis (ALS).
  • 332
  • 30 Aug 2022
Topic Review
Mitochondria in the Central Nervous System
Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA) and mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation. A growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Furthermore, stress, inflammation, mitochondrial impairment have been linked to the activation of the tryptophan–kynurenine metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders.
  • 817
  • 29 Aug 2022
Topic Review
Gamma-Linolenic Acid and Attention Deficit Hyperactivity Disorder
The use of polyunsaturated fatty acids in Attention-Deficit/Hyperactivity Disorder (ADHD) and developmental disorders has been gaining interest with preparations containing different dosages and combinations. Gamma-linolenic acid is an ω-6 fatty acid of emerging interest with potential roles as an adjuvant anti-inflammatory agent that could be used with ω-3 Polyunsaturated fatty acids (PUFAs) in the treatment of ADHD and associated symptoms.
  • 1.0K
  • 26 Aug 2022
Topic Review
Pathophysiological Mechanisms of Antipsychotic-Induced Parkinsonism
Among neurological adverse drug reactions (ADRs) in patients with schizophrenia treated with antipsychotics (APs), drug-induced parkinsonism (DIP) is the most common motility disorder caused by drugs affecting dopamine receptors. One of the causes of DIP is the disruption of neurotransmitter interactions that regulate the signaling pathways of the dopaminergic, cholinergic, GABAergic, adenosinergic, endocannabinoid, and other neurotransmitter systems.
  • 1.0K
  • 26 Aug 2022
Topic Review
Role of NF-kB in Alzheimer’s Disease
Alzheimer’s Disease (AD) is the most common neurodegenerative disease worldwide, with a high prevalence that is expected to double every 20 years. Besides the formation of Aβ plaques and neurofibrillary tangles, neuroinflammation is one the major phenotypes that worsens AD progression. Indeed, the nuclear factor-κB (NF-κB) is a well-established inflammatory transcription factor that fuels neurodegeneration.
  • 1.7K
  • 23 Aug 2022
Topic Review
Music Therapy Intervention in Parkinson’s Disease Patients
Music therapy (MT) is an effective way to treat the gait disorders caused by Parkinson's disease. Rhythm music stimulation, therapeutic singing, and therapeutic instrument performance are often used in clinical practice. The mechanisms of music therapy on the gait of patients with Parkinson's disease include compensation mechanism of cerebellum recruitment, rhythm entrainment, acceleration of motor learning, stimulation of neural coherence, and increase of cortical activity. All mechanisms work together to complete the intervention of MTon patients' gait and help patients to recover better.
  • 754
  • 29 Aug 2022
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