细胞技术

Cell survival and death are complex matters. Too much survival may lead to cancer and too much cell death may result in tissue degeneration. In this chapter, we will first of all focus on the cellular survival mechanisms that promote correct folding and maintenance of protein function. These mecha ...

Amyloid diseases, the most clinically relevant protein misfolding pathologies due to the high prevalence of some of them in the population, are characterized by the presence, in specific tissues and organs, of fibrillar deposits of specific peptides or proteins. Increasing efforts are ...

The unfolded protein response (UPR) was originally identified as a signaling network coordinating adaptive and apoptotic responses to accumulation of unfolded proteins in the endoplasmic reticulum (ER). More recent work has shown that UPR signaling can be triggered by a multitude of c ...

The essential need for mitochondrial function has been extensively shown to relate to neuronal health. Neurodegeneration and neurodegeneration-related diseases have been associated with multiple mitochondrial dysfunctions. This review highlights key findings rela ...

Autophagy is a cellular quality control process by which cytoplasmic constituents including proteins, protein aggregates, organelles, and invading pathogens can be delivered to lysosomes for degradation. Autophagy is activated in response to changes in the internal status of the ...

Cells are under constant onslaught from several intrinsic and extrinsic stressors, which lead to the occurrence and accumulation of molecular damage, functional impairment, aging, and eventual death. Protein misfolding is both a cause and a consequence of increased cellular stress. ...

Mitochondria play a very important role in cellular function, not only through key metabolic reactions and energy generation, but also by being a major site for production of reactive oxygen species and a key player in cell death. Therefore, mitochondrial dysfunction or damage may have severe ...

The upregulation of stress proteins is an important step in the cellular defense against various endogenous and exogenous stressors, and the stress response systems are therefore essential to cell maintenance and survival. In order to evaluate the cellular capability to cope with exog ...

The ambition to measure all or at least a significant fraction of relevant molecules in a cell culture or tissue sample has reached possible realization with the development of the so-called OMICS technologies. We will here briefly review current technologies and give examples of their appl ...

In the cell, the binding of ubiquitin to abnormal or misfolded proteins marks them for degradation by the proteasome or lysosome via autophagy. Ubiquitinated-protein aggregates form when an increase in protein misfolding exceeds the degradation capacity of the cell. Many cellular str ...

The proteasome is an important component of the intracellular system for the turnover of proteins. Themammalian proteasome is engaged to degrade a bulky fraction of soluble intracellular proteins both in an ubiquitin-dependent and independent manner. The proteasome is composed by a ...

Two major proteolysis systems, the ubiquitin-proteasome system, and the autophagy-lysosome system, contribute to degradation of various types of protein and/or protein aggregates. In general, the autophagy-lysosome system is involved in bulk intracellular degradation of p ...

In polyglutamine diseases including Huntington’s disease, the causative gene products containing expanded polyglutamine form nuclear aggregates in neurons. Recent studies have identified several transcriptional factors, which interact with and are sequestered by exp ...

Aberrantly folded proteins and peptides are hallmarks of amyloid diseases. A deeper knowledge of the pathways leading to the formation of amyloid protein aggregates and of the mechanisms of their cytotoxicity is fundamental for a better understanding of several human diseases with am ...

The significance of reactive oxygen species (ROS) as aggravating or primary factors in numerous pathologies is widely recognized, with mitochondria being considered the major intracellular source of ROS. It is not yet possible to routinely measure mitochondrial ROS in animals or cul ...

Mitochondria are the major producers of free radical oxygen species (ROS) as well as the major target of oxidative damage. Defects in the mitochondrial respiratory chain complexes can increase ROS production and reduce ROS removal, leading to oxidative modification of proteins, lipid ...

Glutathione (GSH) is the most abundant antioxidant in aerobic cells, present in micromolar (μM) �concentrations in bodily fluids and in millimolar (mM) concentrations in tissue. GSH is critical for protecting the brain from oxidative stress, acting as a free radical scavenger and inhibi ...

Mitochondria play a number of important roles, including production of ATP for the generation of energy, involvement in the regulation of excitotoxicity, involvement in the homeostasis of intracellular Ca2+, production of reactive oxygen species, and the release of cytochrome c, a pot ...

Cells belonging to the monocyte/macrophage lineage are in general highly resistant to peroxynitrite, a reactive nitrogen species extensively produced by these and other cell types under inflammatory conditions. Resistance is not dependent on the scavenging of peroxynitrite b ...

A central part of the research in protein misfolding and its associated disorders is the development of treatment strategies based on ensuring cellular protein homeostasis. This often includes testing chemical substances or drugs for their ability to counteract protein misfoldi ...