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Topic Review
Alpha-Synuclein in Neurons
Accumulation of the neuronal presynaptic protein alpha-synuclein within proteinaceous inclusions represents the key histophathological hallmark of a spectrum of neurodegenerative disorders, referred to by the umbrella term a-synucleinopathies. Even though alpha-synuclein is expressed predominantly in neurons, pathological aggregates of the protein are also found in the glial cells of the brain. In Parkinson’s disease and dementia with Lewy bodies, alpha-synuclein accumulates mainly in neurons forming the Lewy bodies and Lewy neurites, whereas in multiple system atrophy, the protein aggregates mostly in the glial cytoplasmic inclusions within oligodendrocytes. In addition, astrogliosis and microgliosis are found in the synucleinopathy brains, whereas both astrocytes and microglia internalize alpha-synuclein and contribute to the spread of pathology. The mechanisms underlying the pathological accumulation of alpha-synuclein in glial cells that under physiological conditions express low to non-detectable levels of the protein are an area of intense research. Undoubtedly, the presence of aggregated alpha-synuclein can disrupt glial function in general and can contribute to neurodegeneration through numerous pathways. 
  • 801
  • 17 Jun 2021
Topic Review
Alpha2 Adrenoreceptors in Relation to Spike-wave Epileptic Activity
Spike-wave discharges are the hallmark of idiopathic generalized epilepsy. They are caused by a disorder in the thalamocortical network. Commercially available anti-epileptic drugs have pronounced side effects (i.e., sedation and gastroenterological concerns), which might result from a low selectivity to molecular targets. We suggest a specific subtype of adrenergic receptors (ARs) as a promising anti-epileptic molecular target. The influence of alpha2 ARs is mainly carried out through Gi/o-proteins although coupling to Gs was also demonstrated. Thus, activation of alpha2 ARs can either inhibit or stimulate different intracellular pathways. Numerous neuronal proteins interacting directly or indirectly with alpha2 ARs have been described. Here we describe some mechanisms of noradrenergic modulation of spike-wave activity via ion channels and integral membrane proteins.
  • 481
  • 01 Feb 2023
Topic Review
ALS
The site of origin of amyotrophic lateral sclerosis (ALS), although unsettled, is increasingly recognized as being cortico-fugal, which is a dying-forward process primarily starting in the corticomotoneuronal system. 
  • 1.0K
  • 12 Oct 2021
Topic Review
ALS and NLRP3
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by atrophy and paralysis of voluntary muscles as a result of the progressive loss of upper and lower motor neurons. The best characterized inflammasome is NLRP3, which is composed of the NOD-like receptor pyrin domain containing protein 3, the adaptor protein ASC and pro-caspase 1. Although it has been shown that this inflammasome plays an important role in neurodegenerative disorders, such as multiple sclerosis, Alzheimer’s disease and Parkinson’s disease, little is known about its implication in ALS. Since NLRP3 inflammasome plays a pivotal role in several neurodegenerative disorders, we hypothesized that levels of inflammasome components could help in diagnosis or prognosis of amyotrophic lateral sclerosis (ALS).
  • 610
  • 24 Mar 2021
Topic Review
Alt a 1 Protein Family in Phylogenetic-Related Alternaria
Alternaria is a genus of worldwide fungi found in different habitats such as soil, the atmosphere, plants or indoor environments. Alternaria species are saprobic—largely involved in the decomposition of organic material—but they can also act as animal pathogens, causing disease in humans and animals, developing infections, toxicosis and allergic diseases. A. alternata is considered one of the most important sources of fungal allergens worldwide and it is associated with severe asthma and respiratory status. In fact,  Alt a 1, the main allergen of A. alternata, is an important marker for assessing the risk factor and severity of allergic respiratory disease. Another role of Alt a 1, from a evolutionary point of view, would be to define a family of proteins that would allow establishing taxonomic relationships between different fungal divisions. Finally, Alt a 1 has been shown to be a very useful marker for the identification of pathogenic molds contaminating plants and fruits.
  • 466
  • 28 Apr 2022
Topic Review
ALT Positivity in Human Cancers
Neoplastic cells typically activate one of the two Telomere Maintenance Mechanisms(TMM) to maintain their telomeres during uncontrolled proliferation. Most tumors reactivatetelomerase, a high-fidelity DNA transferase with reverse transcriptase activity. The prevalence of telomerase positive cancers is at 80–90% of all malignancies. A significant percentage of neoplasias activate the second type of TMM, called alternativelengthening of telomeres (ALT), to achieve replicative immortality and telomereelongation. ALT is commonly thought to occur in about 10–20% of all tumors. Unlike the TEL+ tumors, which rely on the enzymatic activity of a single enzyme,ALT relies on many DNA damage response (DDR) proteins, including those involved inthe homology-dependent repair (HDR) pathway.
  • 524
  • 23 Jun 2021
Topic Review
Alteplase
Alteplase (t-PA), a biosynthetic form of human tissue-type plasminogen activator (t-PA), is a thrombolytic medication, used to treat acute ischemic stroke, acute ST-elevation myocardial infarction (a type of heart attack), pulmonary embolism associated with low blood pressure, and blocked central venous catheter. It is given by injection into a vein or artery. Alteplase is the same as the normal human plasminogen activator produced in vascular endothelial cells and is synthesized via recombinant DNA technology in Chinese hamster ovary cells (CHO). Alteplase causes the breakdown of a clot by inducing fibrinolysis.
  • 2.1K
  • 31 Oct 2022
Topic Review
Alterations in the Intestinal Microbiota in ASD
Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system.
  • 197
  • 04 Aug 2023
Topic Review
Alterations in Vascular Chloride Channels and Transporters
Blood pressure is determined by cardiac output and systemic vascular resistance, and mediators that induce vasoconstriction will increase systemic vascular resistance and thus elevate blood pressure. While peripheral vascular resistance reflects a complex interaction of multiple factors, vascular ion channels and transporters play important roles in the regulation of vascular tone by modulating the membrane potential of vascular cells. In vascular smooth muscle cells, chloride ions (Cl−) are a type of anions accumulated by anion exchangers and the anion–proton cotransporter system, and efflux of Cl− through Cl− channels depolarizes the membrane and thereby triggers vasoconstriction. Among these Cl− regulatory pathways, emerging evidence suggests that upregulation of the Ca2+-activated Cl− channel TMEM16A in the vasculature contributes to the increased vascular contractility and elevated blood pressure in hypertension. A robust accumulation of intracellular Cl− in vascular smooth muscle cells through the increased activity of Na+–K+–2Cl− cotransporter 1 (NKCC1) during hypertension has also been reported. Thus, the enhanced activity of both TMEM16A and NKCC1 could act additively and sequentially to increase vascular contractility and hence blood pressure in hypertension.
  • 432
  • 22 Sep 2022
Topic Review
Alterations of Vaginal Microbiota and Chlamydiatrachomatis
Alterations of Vaginal Microbiota and Chlamydia trachomatis as crucial co-causative factors in cervical cancer genesis procured by HPV. Nowadays, it is widely accepted that some types of infections caused by certain viruses, bacteria, and parasites may be the cause of high-risk factors for several types of cancer in humans. These pathogens evolved strategies to hamper the host's integrity of defense such as the prevention of the apoptosis mechanism pathway of the damaged cells reducing the ability to repair the damage(s) and eventually resulting in cellular transformation, cancer progression, and reduced response to therapy.
  • 266
  • 27 Mar 2023
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