Emerging Insights into Prion-Like Degenerative Proteinopathies of the Nervous System

TOPICAL COLLECTIONS

Guest Editors

Asad Jan

Aarhus University

Dr. Asad Jan studied clinical medicine and obtained his PhD in Neuroscience in 2010 from the Swiss Federal Institute of Technology (EPFL) in Switzerland. From 2012 to 2017, he was a postdoctoral fellow at the University of British Columbia, Canada. In late 2017, he joined Aarhus University in Denmark as an AIAS-Marie Curie Research Fellow and continued his independent research. Currently, Dr. Jan is an assistant professor and non-tenured research fellow at Aarhus University, where he receives independent external funding.During these tenures, he has actively collaborated with international teams on mechanistic studies of neurodegenerative diseases, particularly Alzheimer's and Parkinson's. His work includes research on cellular and animal models, phenotype assessment, in-depth histopathological analyses of human and rodent post-mortem tissues, and advanced gene expression profiling using spatial transcriptomics. His complete list of published works can be found on ORCID (0000-0002-3636-0070).

Mette Richner

Aarhus University

Dr. Mette Richner studied molecular biology and earned a PhD in Neuroscience from Aarhus University, Denmark, in 2012, with research stays at MCRI Melbourne, Australia, and L'Institut Universitaire en Santé Mentale de Québec, Canada. From 2012 to 2023, she was a postdoctoral fellow and assistant professor at Aarhus University. Since 2024, Dr. Richner has been working at Aarhus University Core Facilities, advising researchers in imaging and rodent phenotyping. Additionally, she specializes in translating complex scientific topics from technical language into accessible content, often accompanied by scientific illustrations. Her primary research focuses on the cellular and molecular mechanisms underlying neuropathic pain. To this end, she has collaborated extensively with local, national, and international research groups and private pharmaceutical companies.

Collection Overview

Accumulating evidence implicates a prion-like behavior of distinct neuronal proteins in initiating and propagating degenerative pathological processes in the etiology of common neurodegenerative diseases (NDDs). In this regard, a pathogenic role of tau in Alzheimer's disease and other tauopathies, α-synuclein in Parkinson's disease and related synucleinopathies, TDP-43 in frontotemporal dementia and motor neuron disease, and the mutant huntingtin in Huntington's disease are well-established. In particular, several studies in cellular and animal models of common NDDs reinforce the idea that misfolded or aggregation-prone forms or both of these proteins are transmitted between (neuronal or glial) cells, and in some instances, their spreading across neuroanatomical tracts in vivo results in phenotypes, which recapitulate distinct aspects of NDDs symptomatology.

This collection aims to highlight original research, methodological, and technological advances that have improved our understanding of the putative prion-like behavior of protein aggregate pathology. The scope includes, but is not limited to, the following aspects concerning the protein aggregate pathology:

• Methods for the detection of protein aggregate state(s) in tissue specimens, biological fluids, cell and organoid systems, or in vivo animal models (e.g., proximity ligation assays, seed amplification assays, unique molecular tags and/or conformation-specific reagents for in situ imaging)

• Applications of advanced omics methods for characterizing molecular and cellular phenotypes (e.g., spatial transcriptomics, spatial proteomics, multi-omics)

• Biomolecular and functional assays with potential utility in drug discovery and biomarker validation in models of prion-like spreading of protein aggregate pathology

• Advances in the development of animal models (e.g., rodents, C. elegans, Drosophila, fish models), including the study of behaviors and phenotypes relevant to disease symptomatology

• Research containing "negative data" will also be considered upon approval by the editorial team, provided it addresses a significant gap in the methodological and technical knowledge related to the scientific aspects highlighted above.