Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of structure and function of neurons, leading to cognitive decline, motor dysfunction, and ultimately death. Despite significant advances in understanding the genetic and biochemical underpinnings of these diseases, the precise molecular mechanisms driving neurodegeneration remain incompletely understood. This Research Topic seeks to explore the biophysical aspects of neurodegeneration, focusing on the structural, dynamic, and thermodynamic properties of proteins and other biomolecules implicated in neuronal death and dysfunction. The hallmark of many neurodegenerative diseases is the misfolding and aggregation of specific proteins, such as amyloid-beta in Alzheimer’s, alpha-synuclein in Parkinson’s, and huntingtin in Huntington’s disease. These misfolded proteins can form toxic aggregates, including oligomers and fibrils, which disrupt cellular homeostasis and lead to neuronal death.
Biophysical techniques, such as nuclear magnetic resonance (NMR) spectroscopy, cryo-electron microscopy (cryo-EM), and single-molecule fluorescence, have been instrumental in elucidating the structural properties of these aggregates. However, the exact mechanisms by which these aggregates exert their toxic effects remain elusive. Future biophysical studies on neurodegeneration will focus on high-resolution structural analysis of protein aggregates, real-time dynamics of protein misfolding, and the critical interactions between misfolded proteins and cellular membranes. There will be a growing emphasis on understanding the role of liquid-liquid phase separation (LLPS) in the formation of neurotoxic aggregates and using single-molecule techniques to explore the heterogeneity of these processes. Additionally, integrating biophysical data with computational approaches will allow for more accurate predictions of disease progression and therapeutic outcomes.
This Research Topic aims to leverage advanced biophysical methodologies to investigate the molecular mechanisms by which protein misfolding and aggregation contribute to neurodegeneration. The areas covered by this Research Topic may include but are not limited to:
• Structural and dynamic properties of misfolded proteins.
• Advanced biophysical techniques for investigation of amyloid aggregation.
• Role of protein-membrane interactions in neurodegeneration.
• Contribution of liquid-liquid phase separation (LLPS) to the formation of neurotoxic protein aggregates.
• Understanding of protein aggregation by computational approaches
• Identification of potential therapeutic targets based on biophysical insights.
In summary, this series will provide critical biophysical insights into the molecular mechanisms underlying neurodegeneration. By integrating structural biology, thermodynamics, and membrane biophysics, we aim to unravel the complex interplay between protein misfolding, aggregation, and neuronal death, ultimately paving the way for the development of novel therapeutic interventions for neurodegenerative diseases.
Keywords:
protein aggregation, neurodegenerative diseases, molecular biophysics, protein-membrane interaction, structure biology
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.
Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of structure and function of neurons, leading to cognitive decline, motor dysfunction, and ultimately death. Despite significant advances in understanding the genetic and biochemical underpinnings of these diseases, the precise molecular mechanisms driving neurodegeneration remain incompletely understood. This Research Topic seeks to explore the biophysical aspects of neurodegeneration, focusing on the structural, dynamic, and thermodynamic properties of proteins and other biomolecules implicated in neuronal death and dysfunction. The hallmark of many neurodegenerative diseases is the misfolding and aggregation of specific proteins, such as amyloid-beta in Alzheimer’s, alpha-synuclein in Parkinson’s, and huntingtin in Huntington’s disease. These misfolded proteins can form toxic aggregates, including oligomers and fibrils, which disrupt cellular homeostasis and lead to neuronal death.
Biophysical techniques, such as nuclear magnetic resonance (NMR) spectroscopy, cryo-electron microscopy (cryo-EM), and single-molecule fluorescence, have been instrumental in elucidating the structural properties of these aggregates. However, the exact mechanisms by which these aggregates exert their toxic effects remain elusive. Future biophysical studies on neurodegeneration will focus on high-resolution structural analysis of protein aggregates, real-time dynamics of protein misfolding, and the critical interactions between misfolded proteins and cellular membranes. There will be a growing emphasis on understanding the role of liquid-liquid phase separation (LLPS) in the formation of neurotoxic aggregates and using single-molecule techniques to explore the heterogeneity of these processes. Additionally, integrating biophysical data with computational approaches will allow for more accurate predictions of disease progression and therapeutic outcomes.
This Research Topic aims to leverage advanced biophysical methodologies to investigate the molecular mechanisms by which protein misfolding and aggregation contribute to neurodegeneration. The areas covered by this Research Topic may include but are not limited to:
• Structural and dynamic properties of misfolded proteins.
• Advanced biophysical techniques for investigation of amyloid aggregation.
• Role of protein-membrane interactions in neurodegeneration.
• Contribution of liquid-liquid phase separation (LLPS) to the formation of neurotoxic protein aggregates.
• Understanding of protein aggregation by computational approaches
• Identification of potential therapeutic targets based on biophysical insights.
In summary, this series will provide critical biophysical insights into the molecular mechanisms underlying neurodegeneration. By integrating structural biology, thermodynamics, and membrane biophysics, we aim to unravel the complex interplay between protein misfolding, aggregation, and neuronal death, ultimately paving the way for the development of novel therapeutic interventions for neurodegenerative diseases.
Keywords:
protein aggregation, neurodegenerative diseases, molecular biophysics, protein-membrane interaction, structure biology
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.