The lysosome, a membrane-bound organelle, has been classically identified as a terminal degradative centre. The degradative function is dependent on a variety of lysosomal hydrolases and needs an acidic lysosomal luminal pH (~ 4.6). Macromolecule substrates are obtained through endocytosis, phagocytosis or autophagy. By breaking down macromolecules in lysosomes, including proteins, polysaccharides, and complex lipids, their respective constituents such as amino acids (AAs), monosaccharides, and free fatty acids are available for metabolic reutilization. Some lysosomal membrane proteins including ion channels are used for maintaining luminal ionic homeostasis or for signaling, by moving metabolites and ions into or out of this organelle by their electrochemical gradient. Impaired lysosomal ion homeostasis can result in a failure of lysosomes to degrade metabolites, export catabolites and traffic correctly within cells, which may lead to lysosomal storage disorders (LSDs) and neurodegenerative disorders such as Parkinson’s disease Although there are remarkable findings regarding ion channels and transporters on lysosomes, many other lysosomal channels remain unidentified. Thus, it is still largely unclear how lysosomal ion homeostasis is maintained. Therefore, identifying lysosomal channels is an interesting aspect to explore and will greatly enhance our understanding of regulation of the lysosomal ion homeostasis and related disease areas.
Recent technical advances including modified patch-clamp techniques and fluorescence imaging to measure lysosomal membranes and transporters, respectively, have aided the identification of several novel ion channels in the lysosome. Further characterization of lysosome channels and investigation of their cell biological functions is necessary to elucidate the pathogenesis of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease, as well as rare diseases including LSDs and Duchenne muscular dystrophy. Our ultimate goal for this topic section is to lay the groundwork necessary to develop new therapeutic strategies for diseases related to lysosomal channel dysregulation.
This Research Topic welcomes original research, reviews, mini-reviews, and perspectives manuscripts within, but not limited to, the following areas:
1. The function of lysosomal ion channels in neurodegenerative diseases including Alzheimer's Disease and Parkinson's Disease.
2. The function of lysosomal ion channels in rare neurodegenerative diseases including lysosomal storage diseases.
3. Using lysosomal ion channels as therapeutic targets to discover small molecule agonists/antagonist as future drug development.
Keywords:
Ion Channels, Rare Diseases, Neurological Disorders, Neurodegenerative Diseases, Lysosomes
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.
The lysosome, a membrane-bound organelle, has been classically identified as a terminal degradative centre. The degradative function is dependent on a variety of lysosomal hydrolases and needs an acidic lysosomal luminal pH (~ 4.6). Macromolecule substrates are obtained through endocytosis, phagocytosis or autophagy. By breaking down macromolecules in lysosomes, including proteins, polysaccharides, and complex lipids, their respective constituents such as amino acids (AAs), monosaccharides, and free fatty acids are available for metabolic reutilization. Some lysosomal membrane proteins including ion channels are used for maintaining luminal ionic homeostasis or for signaling, by moving metabolites and ions into or out of this organelle by their electrochemical gradient. Impaired lysosomal ion homeostasis can result in a failure of lysosomes to degrade metabolites, export catabolites and traffic correctly within cells, which may lead to lysosomal storage disorders (LSDs) and neurodegenerative disorders such as Parkinson’s disease Although there are remarkable findings regarding ion channels and transporters on lysosomes, many other lysosomal channels remain unidentified. Thus, it is still largely unclear how lysosomal ion homeostasis is maintained. Therefore, identifying lysosomal channels is an interesting aspect to explore and will greatly enhance our understanding of regulation of the lysosomal ion homeostasis and related disease areas.
Recent technical advances including modified patch-clamp techniques and fluorescence imaging to measure lysosomal membranes and transporters, respectively, have aided the identification of several novel ion channels in the lysosome. Further characterization of lysosome channels and investigation of their cell biological functions is necessary to elucidate the pathogenesis of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease, as well as rare diseases including LSDs and Duchenne muscular dystrophy. Our ultimate goal for this topic section is to lay the groundwork necessary to develop new therapeutic strategies for diseases related to lysosomal channel dysregulation.
This Research Topic welcomes original research, reviews, mini-reviews, and perspectives manuscripts within, but not limited to, the following areas:
1. The function of lysosomal ion channels in neurodegenerative diseases including Alzheimer's Disease and Parkinson's Disease.
2. The function of lysosomal ion channels in rare neurodegenerative diseases including lysosomal storage diseases.
3. Using lysosomal ion channels as therapeutic targets to discover small molecule agonists/antagonist as future drug development.
Keywords:
Ion Channels, Rare Diseases, Neurological Disorders, Neurodegenerative Diseases, Lysosomes
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.