Summary: Lewy body dementia ( LBD ) is a challenging-to-diagnose neurodegenerative disease with symptoms similar to both Parkinson’s and Alzheimer’s diseases, including hallucinations, cognitive issues, and movement disorders. Researchers created mini brain models from LBD individual stem cells to mimic vital disease traits found in human brains to research LBD’s progression.
These models helped to identify four potent drugs that might stop the vital protein linked to LBD, alpha-synuclein buildup. The small brains are anticipated to improve the effectiveness of personalized therapy testing and advance our understanding of the disease’s mechanisms. Future research might include developing yet more specific models using more cell types. In the wake of this investigation, LBD may be significantly improved.
Important Information:
- Mini mind models using patient-derived plant cell help imitate LBD growth.
- Four drugs have been identified that could stop damaging alpha-synuclein formation.
- Models provide a program for testing specific procedures and examining disease pathways.
Origin: Mayo Clinic
Lewy body dementia , ( LBD ) is a progressive neurodegenerative disease that shares traits with both , Parkinson’s disease , and , Alzheimer’s disease , but can be more difficult to diagnose. Symptoms may include hallucinations, action disorders, mental issues, sleeping problems and melancholy.
Researchers at Mayo Clinic created little mind models in a dish to better understand how the illness develops, which resemble the features that distinguish Lewy Body dementia patients.
Mini neurons, also known as brain organoids, are lab-grown regions of tissue that mimic the human brains framework. Additionally, the group identified four possible drug combinations that might provide promising treatments for the illness.
Their studies are published in , Science Advances.
There is no treatment for LBD, and professionals claim that there are few reliable experimental models available to study it. A cornerstone of the disorder is a protein called alpha-synuclein, which is encoded by the SNCA protein. This protein is present in brain nerve cells and can grow into people known as Lewy body, which may affect delirium symptoms.
To better comprehend the disease of the condition, a Mayo Clinic study group led by researcher and top author , Na Zhao, M. D., Ph. D. created preliminary mini-brain designs using stem tissues from LBD individuals who had more copies of the SNCA protein, which may have contributed to their problem.
When they were diagnosed while they were still alive, the people donated their body cells. The body cells were then used for analysis by scientists as stem cells.
The researchers demonstrated that their mini-brain designs mirrored changes seen in the human brains of LBD patients who had donated their brains to the Mayo Clinic Brain Bank, making the models useful tools for studying how the condition develops using innovative genetic techniques like single-cell RNA scanning, which examines biological material in unique cells.
The scientists used their tale design program to display nearly 1, 300 Food and Drug Administration-approved medications, identifying four applicants that may help prevent the buildup of alpha-synuclein in neurons.
” This study suggests that these mini-brain models can effectively mimic disease development, providing a potential platform for testing individualized treatments for patients”, says Dr. Zhao.
The four drug candidates that have been identified as potential inhibitors of alpha-synuclein and restore the energy production in LBD patients ‘ neurons could be further refined or modified to create novel treatments for LBD and related dementias in the future.
Additional studies, according to researchers, could introduce additional cell types to better resemble the complexity of the human brain. Researchers could then use these improved models to further investigate disease mechanisms, such as how high-risk genes influence the development of LBD.
About this information on research on brain organs
Author: Lynda De Widt
Source: Mayo Clinic
Contact: Lynda De Widt – Mayo Clinic
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Modeling Lewy body disease with , SNCA , triplication iPSC-derived cortical organoids and identifying therapeutic drugs” by Na Zhao et al. Science Advances
Abstract
Modeling Lewy body disease with , SNCA , triplication iPSC-derived cortical organoids and identifying therapeutic drugs
Aggregated α-synuclein (α-SYN) proteins, encoded by the , SNCA , gene, are hallmarks of Lewy body disease ( LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear.
Here, we recapitulated α-SYN pathologies in human induced pluripotent stem cells (iPSCs ) –derived cortical organoids generated from patients with LBD with , SNCA , gene triplication.
Single-cell RNA sequencing, combined with functional and molecular validation, identified synaptic and mitochondrial dysfunction in excitatory neurons exhibiting high expression of the , SNCA , gene, aligning with observations in the cortex of autopsy-confirmed LBD human brains.
Furthermore, we screened 1280 Food and Drug Administration–approved drugs and identified four candidates ( entacapone, tolcapone, phenazopyridine hydrochloride, and zalcitabine ) that inhibited α-SYN seeding activity in real-time quaking-induced conversion assays with human brains, reduced α-SYN aggregation, and alleviated mitochondrial dysfunction in , SNCA , triplication organoids and excitatory neurons.
Our findings establish human cortical LBD models, and they point to potential therapeutic options for LBD that target -SYN aggregation.
