The dyshomeostasis of the structure and function of a versatile multi-functional RNA/DNA-binding protein, TDP-43, is emerging as an important pathogenic mechanism in ALS and FTLD-TDP diseases. The pathology of TDP-43 proposedly also extends to several other neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The biased cytoplasmic mislocalization of TDP-43 in ALS, which was initially perceived to be pathogenic due to TDP-43 loss-of-function in the nucleus, has, over time, also incorporated toxic gain-of-functions that interfere in the dynamics of several vital cellular sub-structures and physiological processes encompassing, but not limited to, mitochondrial function, stress-granule formation, autophagy, endocytosis and translation. Numerous aberrant post-translational modifications have been uncovered that exacerbate TDP-43 pathology.
The breadth of TDP-43 dyshomeostasis and proteinopathy in neurodegeneration is ever expanding and TDP-43 inclusions have now been reported in several diseases such as ALS, FTLD, Alzheimer’s and Parkinson’s. Thus, understanding and elucidating the intricacies of TDP-43 pathology seems important towards unearthing the convergent toxic pathways across different neurodegenerative diseases.
Contributions that address the mechanisms of TDP-43 misfolding, dyshomeostasis and cytotoxicity using approaches such as genetics, proteomics, genomics, in vitro models, biochemistry and cell biology etc. in any model system are welcomed. As well, manuscripts describing novel strategies to target TDP-43 proteinopathy towards therapeutics of neuro-degenerative diseases, will also be considered.
The dyshomeostasis of the structure and function of a versatile multi-functional RNA/DNA-binding protein, TDP-43, is emerging as an important pathogenic mechanism in ALS and FTLD-TDP diseases. The pathology of TDP-43 proposedly also extends to several other neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The biased cytoplasmic mislocalization of TDP-43 in ALS, which was initially perceived to be pathogenic due to TDP-43 loss-of-function in the nucleus, has, over time, also incorporated toxic gain-of-functions that interfere in the dynamics of several vital cellular sub-structures and physiological processes encompassing, but not limited to, mitochondrial function, stress-granule formation, autophagy, endocytosis and translation. Numerous aberrant post-translational modifications have been uncovered that exacerbate TDP-43 pathology.
The breadth of TDP-43 dyshomeostasis and proteinopathy in neurodegeneration is ever expanding and TDP-43 inclusions have now been reported in several diseases such as ALS, FTLD, Alzheimer’s and Parkinson’s. Thus, understanding and elucidating the intricacies of TDP-43 pathology seems important towards unearthing the convergent toxic pathways across different neurodegenerative diseases.
Contributions that address the mechanisms of TDP-43 misfolding, dyshomeostasis and cytotoxicity using approaches such as genetics, proteomics, genomics, in vitro models, biochemistry and cell biology etc. in any model system are welcomed. As well, manuscripts describing novel strategies to target TDP-43 proteinopathy towards therapeutics of neuro-degenerative diseases, will also be considered.
