Future Directions

Many potential therapeutic treatments for neurodegenerative diseases that reach the clinical trial stage, fail to demonstrate clinical efficacy. In this book chapter we undertook to present the multitude of new multidisciplinary avenues for the treatment of these devastating diseases and hope that one or more of these promising therapies that will dramatically improve the quality of life and long-term survival of those afflicted. It is our expectation and hope that the scientific research devoted to exploring new investigational treatments based on ways to modulate TDP-43 for the alleviation of the suffering of patients with neurodegenerative disorders will result in vast improvements in the clinical course associated with these illnesses for the patient, family and loved ones, and society.
Three of the five available medications — donepezil, galantamine and rivastigmine
— are from a class of drugs called “cholinesterase inhibitors.” These drugs prevent
the breakdown of a chemical messenger in the brain that is important for learning and
memory. The fourth drug, memantine, regulates the activity of a different chemical
messenger in the brain that is also important for learning and memory. Both types of
drugs help manage symptoms but work in different ways. The fifth medication is a
combination of one of the cholinesterase inhibitors (donepezil) with memantine.
Figure attributions :
For ASO:  By Biosyn89 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=23901290
For medicinal plant Vespertunes, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons

Conclusions (10-15 lines)

Acknowledgements:

The author wishes to express her gratitude for the kind reading and discussion of the manuscript with Dr. Manoj Kumar Jaiswal.  

Conflicts of Interests:

The author declares that no competing interests exist and warrants that there are no financial or personal interests, motivations or affiliations that would potentially cause a conflict in the judgments and opinions expressed in this chapter review.  The views and opinions expressed herein do not necessarily reflect the views and opinions of the James J. Peters VA Medical Center or the Icahn  School of Medicine at Mount Sinai. This work is original, non-redundant and has not been duplicated or published elsewhere.

Author Contributions:

This manuscript was conceived, drafted and written exclusively by Pasha Apontes.

Abbreviations:

ALS, amyotrophic lateral sclerosis; APP, amyloid precursor protein; FTD, frontotemporal dementia; transactive response DNA-binding protein gene;  TDP-43, Transactive response DNA-binding protein 43; CTD, C-terminal domain (CTD); NTD, N-terminal domain; NLS, nuclear localization signal; fALS, familial amyotrophic lateral sclerosis; sALS sporatic amyotrophic lateral sclerosis; DSB, double strand break;  RRMI and RRM2, RNA recognition motifs 1 and 2, respectively.