Research Topic

Protein Misfolding and Proteostasis Impairment in Aging and Neurodegeneration: From Spreading Studies to Therapeutic Approaches

About this Research Topic

Misfolding, aggregation, and deposition of proteins in the nervous system are common features of protein misfolding disorders (PMDs). They include several neurodegenerative diseases such as Alzheimer´s disease, Parkinson’s disease, Huntington’s disease, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and prion diseases, among others.

Misfolded proteins are thought to spread/propagate within different anatomical structures of the nervous system through prion-like mechanisms. The seeding-nucleation model provides a plausible explanation on how misfolded aggregates have the intrinsic ability to transmit and propagate a misfolded conformation in vivo. However, how aggregates can spread and progress through the nervous system causing neurodegeneration and the molecular mechanisms underlying this phenomenon remains largely unexplored.

Aging is the most relevant risk factor for many PMDs. Interestingly, recent evidence suggests that the buffering capacity of the proteostasis network decreases with aging contributing to the etiology of these pathologies. However, it remains unknown whether protein misfolding and aggregation are the cause or the consequence of neurodegenerative processes and how changes in the proteostasis during the aging process may facilitate the onset of PMDs.

This Research Topic focuses on protein misfolding and proteostasis impairment in aging and neurodegeneration and aims to provide an overview of the mechanisms rendering neuronal populations vulnerable to proteotoxic stress. Review articles, original research articles and case reports exploring the misfolding and aggregation process of pathological proteins and the decline of proteostasis during aging are especially welcome.

We will also expand the Research Topic by encouraging manuscripts on novel strategies for the treatment of age-dependent protein misfolding disorders targeting distinct components of the proteostasis network.

Potential topics include:

• Misfolding and protein aggregation;
• Pathogenic proteins in PMDs;
• Mechanisms involved in protein spreading;
• Proteostasis in aging;
• Aging process in the context of neurodegeneration;
• Therapeutic approaches.

Topic Editor Dr Rodrigo Morales is an inventor in a patent related to the Protein Misfolding Cyclic Amplification (PMCA) technology, which is currently evaluated as a platform for diagnosis in prion diseases. All other Topic Editors declare no competing interests with regards to the Research Topic subject.


Keywords: protein misfolding, proteostasis, aging, neurodegeneration


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Misfolding, aggregation, and deposition of proteins in the nervous system are common features of protein misfolding disorders (PMDs). They include several neurodegenerative diseases such as Alzheimer´s disease, Parkinson’s disease, Huntington’s disease, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and prion diseases, among others.

Misfolded proteins are thought to spread/propagate within different anatomical structures of the nervous system through prion-like mechanisms. The seeding-nucleation model provides a plausible explanation on how misfolded aggregates have the intrinsic ability to transmit and propagate a misfolded conformation in vivo. However, how aggregates can spread and progress through the nervous system causing neurodegeneration and the molecular mechanisms underlying this phenomenon remains largely unexplored.

Aging is the most relevant risk factor for many PMDs. Interestingly, recent evidence suggests that the buffering capacity of the proteostasis network decreases with aging contributing to the etiology of these pathologies. However, it remains unknown whether protein misfolding and aggregation are the cause or the consequence of neurodegenerative processes and how changes in the proteostasis during the aging process may facilitate the onset of PMDs.

This Research Topic focuses on protein misfolding and proteostasis impairment in aging and neurodegeneration and aims to provide an overview of the mechanisms rendering neuronal populations vulnerable to proteotoxic stress. Review articles, original research articles and case reports exploring the misfolding and aggregation process of pathological proteins and the decline of proteostasis during aging are especially welcome.

We will also expand the Research Topic by encouraging manuscripts on novel strategies for the treatment of age-dependent protein misfolding disorders targeting distinct components of the proteostasis network.

Potential topics include:

• Misfolding and protein aggregation;
• Pathogenic proteins in PMDs;
• Mechanisms involved in protein spreading;
• Proteostasis in aging;
• Aging process in the context of neurodegeneration;
• Therapeutic approaches.

Topic Editor Dr Rodrigo Morales is an inventor in a patent related to the Protein Misfolding Cyclic Amplification (PMCA) technology, which is currently evaluated as a platform for diagnosis in prion diseases. All other Topic Editors declare no competing interests with regards to the Research Topic subject.


Keywords: protein misfolding, proteostasis, aging, neurodegeneration


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

09 June 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

09 June 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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