Lipids are the most abundant organic molecule found in the brain. Thus, their quantity, organization, biosynthesis, and metabolism are crucial for the normal function of neuronal cells. Lipid molecules are the main component of biological membranes and ascertain the emplacement and function of cell-membrane-located proteins. Mutual interaction between lipids and proteins contribute in membrane remodelling, regulation of synaptic signalling, and membrane trafficking in neurons. Such interactions play important role in inflammation, oxidation, myelination, and energy balance of neuronal cells. Some variety of lipid molecules acts as transmitters and conveys signals in intra- or inter-cellular context. In neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease misfolded peptide aggregates are hallmarks of the disease pathology. Lipids are known to activate ß-amyloid and a-synuclein peptide aggregation. Moreover, association of misfolded proteins to membrane lipids entails intracellular damages. Understanding interaction of these aggregates with cell membrane lipid molecules is a fertile research area that can reveal essential clues underlie proteinopathies and pave the way for development of effective therapeutic interventions.
Although the growing body of studies illustrates some aspects of ß-amyloid, alpha-synuclein, and Tau peptides' interactions with membrane lipid molecules of neurons, the complete scenario leading to neuronal demise needs to be studied yet. Aß peptides are products of amyloid precursor protein (APP) cleavage by beta and gamma secretases. Aß peptides can insert or bind to membrane lipids. These interactions lead to membrane permeabilization and Aß fibril aggregation, respectively. alpha-synuclein can undergo alpha-helical folding once associated with lipid membranes. Hyperphosphorylation of Tau reduces its affinity to microtubules. The released Tau proteins can interact with the membrane and form tau-phospholipid complexes which trigger the formation of neurofibrillary tangles. Amyloid plaques, alpha-synuclein aggregates and Tau tangles share a feature in common and mainly affect synaptic terminals and disrupt neuronal connections. Lipids play a vital role in normal synaptic functions. Apolipoprotein E (APOE) is the main lipoprotein in human brain deals with neuron-glia lipid transfer and lipid metabolism. Epsilon 4 (E4) isoform of is the strongest known genetic risk factor for Alzheimer’s disease development among elder populations. Moreover, abnormal lipid metabolism can directly affect the lipid composition of the mitochondrial inner membrane and consequently alter the function of protein complexes of the electron transfer chain which may result in oxidative stress and lipid peroxidation. Knowing more about interaction of proteins with lipid molecules and regulation of such interactions is the major goal of this research topic.
The aim of this Research Topic is to strengthen our understanding of the lipid-protein interactions and regulation in neurodegenerative disorders and introduce novel, advanced and applicable methods for such investigations. By this means we welcome contributions of Original Research, Systematic Reviews, Methods, Review, Mini Review, Perspective, and Brief Research Report articles that cover, but are not limited to, the following topics:
1. The nature of misfolded protein interactions with membrane lipids.
2. Regulation of lipid-protein interactions.
3. Consequent molecular and cellular events of lipid-protein interactions underlying neurodegenerative diseases.
4. Lipidomics of neurons in neurodegenerative conditions.
5. Development of techniques and methods to study lipid-protein interactions.
6. Therapeutic strategies to manage neurodegeneration targeting lipid molecules.
Lipids are the most abundant organic molecule found in the brain. Thus, their quantity, organization, biosynthesis, and metabolism are crucial for the normal function of neuronal cells. Lipid molecules are the main component of biological membranes and ascertain the emplacement and function of cell-membrane-located proteins. Mutual interaction between lipids and proteins contribute in membrane remodelling, regulation of synaptic signalling, and membrane trafficking in neurons. Such interactions play important role in inflammation, oxidation, myelination, and energy balance of neuronal cells. Some variety of lipid molecules acts as transmitters and conveys signals in intra- or inter-cellular context. In neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease misfolded peptide aggregates are hallmarks of the disease pathology. Lipids are known to activate ß-amyloid and a-synuclein peptide aggregation. Moreover, association of misfolded proteins to membrane lipids entails intracellular damages. Understanding interaction of these aggregates with cell membrane lipid molecules is a fertile research area that can reveal essential clues underlie proteinopathies and pave the way for development of effective therapeutic interventions.
Although the growing body of studies illustrates some aspects of ß-amyloid, alpha-synuclein, and Tau peptides' interactions with membrane lipid molecules of neurons, the complete scenario leading to neuronal demise needs to be studied yet. Aß peptides are products of amyloid precursor protein (APP) cleavage by beta and gamma secretases. Aß peptides can insert or bind to membrane lipids. These interactions lead to membrane permeabilization and Aß fibril aggregation, respectively. alpha-synuclein can undergo alpha-helical folding once associated with lipid membranes. Hyperphosphorylation of Tau reduces its affinity to microtubules. The released Tau proteins can interact with the membrane and form tau-phospholipid complexes which trigger the formation of neurofibrillary tangles. Amyloid plaques, alpha-synuclein aggregates and Tau tangles share a feature in common and mainly affect synaptic terminals and disrupt neuronal connections. Lipids play a vital role in normal synaptic functions. Apolipoprotein E (APOE) is the main lipoprotein in human brain deals with neuron-glia lipid transfer and lipid metabolism. Epsilon 4 (E4) isoform of is the strongest known genetic risk factor for Alzheimer’s disease development among elder populations. Moreover, abnormal lipid metabolism can directly affect the lipid composition of the mitochondrial inner membrane and consequently alter the function of protein complexes of the electron transfer chain which may result in oxidative stress and lipid peroxidation. Knowing more about interaction of proteins with lipid molecules and regulation of such interactions is the major goal of this research topic.
The aim of this Research Topic is to strengthen our understanding of the lipid-protein interactions and regulation in neurodegenerative disorders and introduce novel, advanced and applicable methods for such investigations. By this means we welcome contributions of Original Research, Systematic Reviews, Methods, Review, Mini Review, Perspective, and Brief Research Report articles that cover, but are not limited to, the following topics:
1. The nature of misfolded protein interactions with membrane lipids.
2. Regulation of lipid-protein interactions.
3. Consequent molecular and cellular events of lipid-protein interactions underlying neurodegenerative diseases.
4. Lipidomics of neurons in neurodegenerative conditions.
5. Development of techniques and methods to study lipid-protein interactions.
6. Therapeutic strategies to manage neurodegeneration targeting lipid molecules.
