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Pathological aggregates of alpha-synuclein are the common hallmarks of synucleinopathies, including Parkinson's disease. There is currently no disease-modifying therapy approved for neurodegenerative synucleinopathies. The induction of macroautophagy by small compounds may be a strategy to reduce the cellular alpha-synuclein burden and to confer neuroprotection. Therefore, in the present study, we investigated a broad spectrum of druggable molecular signaling pathways reported to induce macroautophagy in human cells and compared their protective efficacy against alpha-synuclein-induced toxicity in cultured human postmitotic dopaminergic neurons. Several compounds affecting different pathways were able to activate macroautophagy. All compounds that activated autophagy also protected against alpha-synuclein-induced toxicity. The compounds with the lowest effective concentrations were PI-103, L-690,330, and NF 449, making them particularly interesting for further investigations, including in vivo models. Our findings demonstrate that activation of macroautophagy, as a neuroprotective approach in synucleinopathies, is accessible to pharmacotherapy. Moreover, pharmacological activation of macroautophagy via diverse signaling pathways is effective to protect human dopaminergic neurons against alpha-synuclein-induced toxicity.
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The current study was carried out to investigate the serum and synovial fluid (SF) alpha-melanocyte-stimulating hormone (α-MSH) levels in correlation with disease severity in primary knee osteoarthri...
Autophagy mediates the delivery of cytoplasmic content to vacuoles or lysosomes for degradation or storage. The best characterized autophagy route called macroautophagy involves the sequestration of c...
Macroautophagy is a ubiquitous degradative pathway involved in innate and adaptive immunity. Its molecular machinery has been described to deliver intracellular and extracellular antigens to MHC class...
Vitamins are among the most frequently used supplements (48% of US adults). However, little is known about contributions of genetic variation to their efficacy and safety. Multiple pathways link catec...
Alpha-synuclein oligomers are thought to be toxic mediators of Parkinson's disease and other alpha-synucleinopathies, but their histological detection in situ in diseased brain has been a challenge in...
OBJECTIVES: I. Determine the maximum tolerated dose and safety of alpha-melanocyte stimulating hormone (alpha-MSH) in patients with acute renal failure. II. Determine the safety and ph...
Multiple pathways including peripheral and central hormones and neurotransmitters are involved in the regulation of food intake and body weight. One of the most studied pathways involves ...
The purpose of this study is gain a better understanding of a molecule called alpha melanocyte stimulating hormone (alpha MSH) and its potential role in your retinal disease. Alpha MSH has...
Most neurological and neurodegenerative diseases have a multifactorial nature. For some of them it is documented a genetic component (sometimes described as Mendelian, other times as a mul...
This study will see if interferon-alpha given early in the disease can stop or slow the immune attack on insulin-producing cells. In addition, the study will examine the safety and efficac...
Signaling proteins which function as master molecular switches by activating Rho GTPases through conversion of guanine nucleotides. Rho GTPases in turn control many aspects of cell behavior through the regulation of multiple downstream signal transduction pathways.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
A major gonadotropin secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and the LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. The alpha subunit is common in the three human pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.
A liver microsomal cytochrome P450 enzyme that catalyzes the 12-alpha-hydroxylation of a broad spectrum of sterols in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP8B1gene, converts 7-alpha-hydroxy-4-cholesten-3-one to 7-alpha-12-alpha-dihydroxy-4-cholesten-3-one and is required in the synthesis of BILE ACIDS from cholesterol.
Parkinson's is a progressive neurological condition, affecting one person in every 500, 95% of which are over 40. It is caused by degeneration of more than 70% of the substantia nigra, which depletes the dopamine (the neurotransmitter involved in pro...