Brain Organoid Model Systems of Neurodegenerative Diseases: Recent Progress and Future Prospects

Saniyah Shaikh¹Luqman Siddique¹Hafsah T Khalifey¹Rutaba Mahereen¹Thaabit Raziq¹Rushdan M Firdous¹Aisha Siddique^1,2Ismail M Shakir^1,2Zara Ahmed¹Arshiya Akbar³Eman A Alshehri⁴Raja Chinnappan¹Alaa Alzhrani^1,4,5Tanveer Ahmed Mir^1,4Ahmed Yaqinuddin^6*

• ¹College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
• ²King Abdullah University of Science and Technology, Thuwal, Makkah, Saudi Arabia
• ³Osmania University, Hyderabad, Telangana, India
• ⁴Organ Transplant Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
• ⁵King Abdulaziz University, Jeddah, Makkah, Saudi Arabia
• ⁶Alfaisal University, Riyadh, Saudi Arabia

Neurological diseases are a leading cause of disability, morbidity, and mortality, affecting 43% of the world's population. The detailed study of neurological diseases, testing of drugs, and repair of sitespecific defects require physiologically relevant models that recapitulate key events and dynamic neurodevelopmental processes in a highly organized fashion. As an evolving technology, selforganizing and self-assembling brain organoids offer the advantage of modeling different stages of brain development in a 3D microenvironment. Herein, we review the utility, advantages, and limitations of the latest breakthroughs in brain organoid endeavors in the context of modeling three of the most prevalent neurodegenerative diseases -Alzheimer's, Parkinson's, and Huntington's disease.We conclude the review with a perspective on the future prospects of brain organoid models with their myriad possible applications in translational medicine.