About this Research Topic
The level of each protein in a eukaryotic cell is optimized for its physiological functions, determined by the combined rates of its synthesis and degradation. Proteins are synthesized when their mRNA transcripts are translated by ribosomes. Nascent proteins undergo folding, posttranslational modification, and subcellular trafficking to reach their functional destinations. Expired or damaged proteins are identified by quality control mechanisms and targeted for degradation by the ubiquitin-proteasome system and autophagy. The resulting steady state of the proteome in healthy cells is known as proteostasis.
Loss of proteostasis is a common condition that contributes to the pathology of various diseases. Among the different cell types in eukaryotic organisms, long-lived neurons are particularly vulnerable to proteostasis deregulation, which takes a long time to develop. Consistent with this, aging is the main risk factor for human neurodegenerative diseases linked to a global dysregulation of neuronal proteostasis. Therefore, breakthroughs in treating neurodegenerative diseases can be achieved through a better understanding of the molecular and cellular mechanisms underlying the dysregulation of neuronal proteostasis.
A growing body of evidence implicates aberrant proteins in the dysregulation of cellular proteostasis. Proteins misfolded due to genetic mutations or environmental factors can form amyloid aggregates through a multi-step process, making them resistant to degradation. These cytotoxic amyloids and their precursors can inhibit proteasomal and autophagic pathways, impair synaptic and mitochondrial functions, and induce oxidative stress, ultimately leading to neuronal dysfunction and death. For instance, amyloid-beta and tau proteins are well-known to form such aggregates in Alzheimer's disease, while comparable intracellular inclusions are observed for synuclein in forms of Parkinson’s disease and polyglutamine-expanded proteins in the respective polyglutamine diseases. Furthermore, misfolded proteins can trigger inflammatory responses by activating microglia and astrocytes, exacerbating neuronal damage.
We invite original research articles, reviews, mini-reviews, brief research reports, and perspectives addressing the pathological mechanisms responsible for the loss of neuronal proteostasis and its consequences for the development of neurodegenerative diseases. Groundbreaking research aimed at developing novel therapeutic approaches using in vitro and in vivo systems, and animal models, is highly encouraged. While the focus is on the following cellular processes involved in proteostasis, any new directions will be carefully considered:
• Protein folding and molecular chaperones
• Protein-unfolding ATPases
• Posttranslational processing, including proteolytic fragmentation
• Protein trafficking
• The Ubiquitin Proteasome System (UPS)
• Autophagy
• Mitochondrial proteostasis
• Proteostasis-linked transcriptional mechanisms
Loss of proteostasis is a common condition that contributes to the pathology of various diseases. Among the different cell types in eukaryotic organisms, long-lived neurons are particularly vulnerable to proteostasis deregulation, which takes a long time to develop. Consistent with this, aging is the main risk factor for human neurodegenerative diseases linked to a global dysregulation of neuronal proteostasis. Therefore, breakthroughs in treating neurodegenerative diseases can be achieved through a better understanding of the molecular and cellular mechanisms underlying the dysregulation of neuronal proteostasis.
A growing body of evidence implicates aberrant proteins in the dysregulation of cellular proteostasis. Proteins misfolded due to genetic mutations or environmental factors can form amyloid aggregates through a multi-step process, making them resistant to degradation. These cytotoxic amyloids and their precursors can inhibit proteasomal and autophagic pathways, impair synaptic and mitochondrial functions, and induce oxidative stress, ultimately leading to neuronal dysfunction and death. For instance, amyloid-beta and tau proteins are well-known to form such aggregates in Alzheimer's disease, while comparable intracellular inclusions are observed for synuclein in forms of Parkinson’s disease and polyglutamine-expanded proteins in the respective polyglutamine diseases. Furthermore, misfolded proteins can trigger inflammatory responses by activating microglia and astrocytes, exacerbating neuronal damage.
We invite original research articles, reviews, mini-reviews, brief research reports, and perspectives addressing the pathological mechanisms responsible for the loss of neuronal proteostasis and its consequences for the development of neurodegenerative diseases. Groundbreaking research aimed at developing novel therapeutic approaches using in vitro and in vivo systems, and animal models, is highly encouraged. While the focus is on the following cellular processes involved in proteostasis, any new directions will be carefully considered:
• Protein folding and molecular chaperones
• Protein-unfolding ATPases
• Posttranslational processing, including proteolytic fragmentation
• Protein trafficking
• The Ubiquitin Proteasome System (UPS)
• Autophagy
• Mitochondrial proteostasis
• Proteostasis-linked transcriptional mechanisms
Keywords: proteostasis, neurodegeneration, ubiquitin, trascriptional mechanisms, proteolytic fragmentation, molecular chaperones, Protein-unfolding ATPases, autophagy, Mitochondrial proteostasis
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