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
Oxidative Stress, NAD+ in ASL
ALS, often referred to as “Lou Gehrig’s disease”, is a progressive neurodegenerative disease that damages motor neurons (MNs) in the brain and the spinal cord. This loss of MNs is responsible for progressive weakness and paralysis. There is mounting evidence involving oxidative stress as a main pathophysiological mechanism leading to MN damage and death. Conceptually, oxidative stress is an imbalance of oxygen-derived free radicals and antioxidants in the body, which can lead to cell and organ damage. Reactive oxygen species (ROS) contain an uneven number of electrons and, at high non-physiological levels, can cause oxidative damages to nucleic acids, lipids, and proteins. Moreover, the generation of NO and H2O2 (induced by proinflammatory cytokines in e.g., endothelial cells) can lead to the formation of highly damaging –OONO radicals. On the other hand, NAD+ is involved in cell bioenergetics, redox regulation, signaling, homeostasis, adaptive response to stress, and survival. Specifically, different NAD+-dependent enzymes are implicated in mechanisms regulating synaptic plasticity and neuronal resilience to stress.
  • 617
  • 03 Sep 2021
Topic Review
Exercise and Parkinson’s Neural Mitochondria
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.
  • 437
  • 17 Aug 2021
Topic Review
LRRK2 in Parkinson’s Disease
LRRK2 is a large (2527 amino acids, 286 kDa), multidomain protein, that bears two enzymatic functions: kinase and GTPase, and several protein-protein interaction domains. Numerous genomic LRRK2 variants have been repeatedly confirmed as pathogenic in Parkinson's Disease (PD). Inhibition of LRRK2 was shown to rescue neurite shortening caused by PD mutations in this protein. This entry discusses possible ways of targetting LRRK2 as potential treatment for PD.
  • 556
  • 09 Aug 2021
Topic Review
Pathophysiology of ALS
Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system. It is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and paralysis. ALS is incurable and has a bleak prognosis, with median survival of 3–5 years after the initial symptomatology.
  • 635
  • 26 Jul 2021
Topic Review
Seizures and Newborn Infants
Seizures are common in newborn infants with hypoxic-ischemic encephalopathy and are highly associated with adverse neurodevelopmental outcomes. The impact of seizure activity on the developing brain and the most effective way to manage these seizures remain surprisingly poorly understood, particularly in the era of therapeutic hypothermia. Critically, the extent to which seizures exacerbate brain injury or merely reflect the underlying evolution of injury is unclear. Current anticonvulsants, such as phenobarbital and phenytoin have poor efficacy and preclinical studies suggest that most anticonvulsants are associated with adverse effects on the developing brain. Levetiracetam seems to have less potential neurotoxic effects than other anticonvulsants but may not be more effective. Given that therapeutic hypothermia itself has significant anticonvulsant effects, randomized controlled trials of anticonvulsants combined with therapeutic hypothermia, are required to properly determine the safety and efficacy of these drugs. Small clinical studies suggest that prophylactic phenobarbital administration may improve neurodevelopmental outcomes compared to delayed administration; however, larger high-quality studies are required to confirm this. In conclusion, there is a distinct lack of high-quality evidence for whether and to what extent neonatal seizures exacerbate brain damage after hypoxia-ischemia and how best to manage them in the era of therapeutic hypothermia. 
  • 515
  • 22 Jul 2021
Topic Review
Therapy for Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease characterized by the selective loss of motor neurons in the spinal cord and motor cortex. Muscle weakness and degradation at 2–5 years after the onset of symptoms can result in fatal muscle dystrophy, paralysis, and death. Most ALS cases (90–95%) occur sporadically with no clearly related risk factors, while approximately 5–10% of ALS cases are considered to be hereditary, attributed to various mutations in specific genes.
  • 553
  • 19 Jul 2021
Topic Review
Neural Stem Cell-Based Therapy
Transplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challenges are yet to be overcome to reach clinical applications. The major limitation of the NSC-based therapy is its inability to retain most of the donor stem cells after grafting into an ischemic brain area which is lacking of essential oxygen and nutrients for the survival of transplanted cells. Low cell survival rate limits the capacity of NSCs to repair the injured area and this poses a much more difficult challenge to the NSC-based therapy for ischemic stroke. In order to enhance the survival of transplanted cells, several stem cell culture preconditioning strategies have been employed. For ischemic diseases, hypoxic preconditioning is the most commonly applied strategy since the last few decades. Now, the preconditioning strategies have been developed and expanded enormously throughout years of efforts. This entry systematically presented studies searched from PubMed, ScienceDirect, Web of Science, Scopus and the Google Scholar database up to 31 March 2020 based on search words containing the following terms:“precondition” or “pretreatment” and “neural stem cell” and “ischemic stroke”. The searched data comprehensively reported seven major NSC preconditioning strategies including hypoxic condition, small drug molecules such as minocycline, doxycycline, interleukin-6, adjudin, sodium butyrate and nicorandil, as well as electrical stimulation using conductive polymer for ischemic stroke treatment. We discussed therapeutic benefits gained from these preconditioned NSC for in vitro and in vivo stroke studies and the detailed insights of the mechanisms underlying these preconditioning approaches. Nonetheless, there was a scarcity of evidence on the ecacy of these preconditioned NSCs in human clinical studies, therefore, it is still too early to draw a definitive conclusion on the efficacy and safety of this active compound for patient usage. Thus, we suggest for more in-depth clinical investigations of this cell-based therapy to develop into more conscientious and judicious evidence-based therapy for clinical application in the future.
  • 459
  • 02 Jul 2021
Topic Review
Commonalities in Amyloid Prefibrillar Oligomers
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.
  • 704
  • 02 Jul 2021
Topic Review
Ceramide Metabolism and Parkinson’s Disease
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. 
  • 733
  • 30 Jun 2021
Topic Review
Neurodegeneration in NPC Disease
Niemann–Pick type C (NPC) disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol in the late endo-lysosomal system of cells. Progressive neurological deterioration and the onset of symptoms, such as ataxia, seizures, cognitive decline, and severe dementia, are pathognomonic features of the disease. In addition, different pathological similarities, including degeneration of hippocampal and cortical neurons, hyperphosphorylated tau, and neurofibrillary tangle formation, have been identified between NPC disease and other neurodegenerative pathologies.
  • 875
  • 22 Jun 2021
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