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Topic Review
Nanobodies
Nanobodies are highly water-soluble and stable, have high specificity, and can bind their targets with very high affinity, often in the low nanomolar range. 
  • 1.5K
  • 10 May 2021
Topic Review
Senescent Microglia
Microglia, far from being simply ‘brain glue’, play an important role as the brain’s resident immune cells. Their roles include phagocytic clearance of debris, pruning of synapses, and possibly even contributing to synaptic activity, being of critical importance from early development to ageing. Despite being such long-lived cells, microglia have been relatively understudied for their role in the ageing process. Reliably identifying aged microglia has proven challenging, not least due to the diversity of cell populations, and the limitations of available models, further complicated by differences between human and rodent cells.
  • 652
  • 07 May 2021
Topic Review
Redox Homeostasis in Pancreatic β-Cells
Redox status is a key determinant in the fate of every cell, β-cell in particular.  β-cells are not primarily detoxifying like e.g. hepatocytes or kidney cells and thus do not possess extensive antioxidant defense machinery. However, they show a wide range of redox regulating proteins, such as peroxiredoxins, thioredoxins or thioredoxin reductases, etc., being functionally compartmentalized. These proteins keep fragile redox homeostasis and serve as messengers and amplifiers of redox signaling which is inevitable for proper β-cell function (particularly insulin secretion) and maintenance. Dysbalance in redox homeostasis establishes oxidative stress which accompanies the development of type 2 diabetes.
  • 423
  • 06 May 2021
Topic Review
Precision Oncology Beyond Genomics
Cancer is a multifactorial disease with increasing incidence. There are more than 100 different cancer types, defined by location, cell of origin, and genomic alterations that influence oncogenesis and therapeutic response. This heterogeneity between tumors of different patients and also the heterogeneity within the same patient’s tumor pose an enormous challenge to cancer treatment.
  • 419
  • 06 May 2021
Topic Review
VEGF
VEGF-A (also called VEGF) is a member of the mammalian platelet-derived growth factor (PDGF) supergene family which also includes VEGF-B, VEGF-C, VEGF-D and placental growth factor (PlGF).
  • 761
  • 05 May 2021
Topic Review
Deubiquitinases in Regulated Cell Death
The mechanisms and physiological implications of regulated cell death (RCD) have been extensively studied. Among the regulatory mechanisms of RCD, ubiquitination and deubiquitination enable post-translational regulation of signaling by modulating substrate degradation and signal transduction. Deubiquitinases (DUBs) are involved in diverse molecular pathways of RCD. Some DUBs modulate multiple modalities of RCD by regulating various substrates and are powerful regulators of cell fate.
  • 533
  • 05 May 2021
Topic Review
Invertebrate Models Untangle PD Mechanism
Parkinson’s disease (PD) is the second most common neurodegenerative disease, afflicting ~10 million people worldwide. Although several genes linked to PD are currently identified, PD re-mains primarily an idiopathic disorder. Neuronal protein α-synuclein is a major player in disease progression of both genetic and idiopathic forms of PD. However, it cannot alone explain under-lying pathological processes. Recent studies demonstrate that many other risk factors can acceler-ate or further worsen brain dysfunction in PD patients. Several PD models, including non-mammalian eukaryotic organisms, have been developed to identify and characterize these factors.
  • 312
  • 03 May 2021
Topic Review
Uncoupling Aging from Chronological Time
Cellular life evolved from simple unicellular organisms that could replicate indefinitely, being essentially ageless. At this point, life split into two fundamentally different cell types: the immortal germline representing an unbroken lineage of cell division with no intrinsic endpoint and the mortal soma, which ages and dies. We consider aging as a process not fixed to the pace of chronological time but one that can speed up or slow down depending on the rate of intrinsic cellular clocks. Moreover germline factor reprogramming might be used to slow the rate of aging and potentially reverse it by causing the clocks to tick backward. Therefore, reprogramming may eventually lead to therapeutic strategies to treat degenerative diseases by altering aging itself, the one condition common to us all.
  • 519
  • 02 May 2021
Topic Review
Multidrug Resistance Mechanisms and Nano-Treatments
The cellular mechanisms of drug resistance prevent the correct efficacy of the therapies used in various types of cancer and nanotechnology has been postulated as a possible alternative to avoid them. This entry focuses on describing the different mechanisms of drug resistance and dis-covering which nanotechnology-based therapies have been used in recent years to evade them in colon (CRC) and pancreatic cancer (PAC). Here we summarize the use of different types of nanotechnology (mainly nanoparticles) that have shown efficacy in vitro and in vivo in preclinical phases, allowing future in-depth research in CRC and PAC and its translation to future clinical trials.
  • 509
  • 02 May 2021
Topic Review
Breakdown of Filamentous Myofibrils
Protein degradation maintains cellular integrity by regulating virtually all biological pro- cesses, whereas impaired proteolysis perturbs protein quality control, and often leads to human disease. Two major proteolytic systems are responsible for protein breakdown in all cells: autophagy, which facilitates the loss of organelles, protein aggregates, and cell surface proteins; and the ubiquitin-proteasome system (UPS), which promotes degradation of mainly soluble proteins. Recent findings indicate that more complex protein structures, such as filamentous assemblies, which are not acces- sible to the catalytic core of the proteasome in vitro, can be efficiently degraded by this proteolytic machinery in systemic catabolic states in vivo. Mechanisms that loosen the filamentous structure seem to be activated first, hence increasing the accessibility of protein constituents to the UPS. In this review, we will discuss the mechanisms underlying the disassembly and loss of the intricate insoluble filamentous myofibrils, which are responsible for muscle contraction, and whose degradation by the UPS causes weakness and disability in aging and disease. Several lines of evidence indicate that myofibril breakdown occurs in a strictly ordered and controlled manner, and the function of AAA-ATPases is crucial for their disassembly and loss.
  • 610
  • 30 Apr 2021
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