Synopsis :
The spread of harmful alpha-synuclein proteins in Parkinson’s disease was found to be caused by the Aplp1 protein, according to the researchers. In particular, a cancer medication that has received FDA approval has a significant impact by specifically targeting the protein Lag3 and preventing its interaction with Aplp1, which stops the disease from progressing in mice models. This cutting-edge research has produced a brilliant concept for expanding the application of currently available cancer treatments to Parkinson’s disease and other neurological diseases.
Evaluation:
This article provides a thorough analysis and knowledge of the function that the interaction between Aplp1 and lag3 plays in the progression of Parkinson’s disease, as well as the importance of cancer treatments in halting the disease’s progression.
Strategies for research:
Genetically engineered mice were used for research. Aplp, a cell surface protein that is responsible for spreading harmful alpha synuclein in Parkinson disease, was identified by Johns Hopkins researchers. The role of lag3 binding with alpha synuclein protein was discovered in Mao and Dawson’s mice model investigations, which were published in 2016 and 2021.Their research also showed that the cells’ absorption of these dangerous proteins is caused by another protein. According to Valina Dawson, researchers used genetically engineered mice lacking either Aplp1 or Lag3, or both, and found that there was a significant decrease in harmful alpha synuclein protein. This indicates that the Aplp1 protein may be the reason for the recent experiments, as previous research had shown that Lag-3 alone was not responsible for the absorption of alpha synuclein by neurons. Researchers found that giving Lag 3 antibody injections to mice greatly decreased the connection between Aplp1 and Lag3, which causes neurons to inhibit harmful
proteins.
Significance :
Research has demonstrated novel approaches to treating Parkinson’s disease using currently available cancer treatments, and it will pave the path for new discoveries and improved prognosis for Parkinson’s disease and other neurodegenerative disorders. The FDA-approved cancer treatment medicines relamimab and nivolumab block alpha synuclein absorption.
Interpretation:
The interaction between Lag 3 and a
Aplp1 is crucial in Parkinson disease. The FDA-approved cancer medication contributes significantly by focusing on the Lag3. Researchers at Johns Hopkins have discovered that the alpha synuclein protein is a dangerous protein that attacks brain cells and kills those that produce the neurotransmitter dopamine, which causes Parkinson’s disease to worsen. Parthanatos, the Greek word for “death,” is the process that results in impairments to intellect, movement, and emotional control. Only through their interaction with Lag 3 and Aplp3 are these proteins absorbed by healthy brain cells. Proteins, which become misfolded and aggregate in neurons. The protein Aplp1 facilitates the binding of Lag3 to alpha synuclein, which spreads throughout the brain’s cells and kills them. Pathologic alpha synuclein binding, internalization, and transmission are caused by the interaction of the Aplp1 protein with Lag3. Anti-Lag 3 antibodies work by interfering with the interaction between Lag3 and Aplp1 proteins. This prevents the internalization of alpha syn-performed fibril protein, which in turn stops the death of dopaminergic neurons.
Impact:
Mao states that this finding holds significant potential for treating neurodegenerative diseases for which there is presently no treatment.
Alzheimer’s disease symptoms include memory loss, mood instability, and physical issues. This disease is caused by tau proteins, which become misfolded and aggregate in neurons. The tau protein linked to dementia is captured by the lag3 antibody, which has an essential effect on Alzheimer’s disease.
Ted Dawson made the decision to conduct trials on mice with Parkinson’s and Alzheimer’s disease in view of the lag3 antibody’s success rate in those mice.
Significant Technologies:
Parkinson’s disease: It is a degenerative illness that impacts dopamine-generating cells in the substantia nigra, a specific brain region. The reduction in dopamine levels is the primary cause of many symptoms of Parkinson’s disease. The symptoms develop gradually over time and vary from person to person.
Alzheimer’s Disease: Alzheimer’s disease is a neurodegenerative disease that involves parts of the brain that control thought, memory, and language. This is the most common form of dementia that typically develops slowly and worsens over time.
APLP1: The APLP 1 gene is responsible for the expression of amyloid-like protein 1 (APLP1) in humans. They play a significant role in modulating insulin and glucose homeostasis.
LAG3: Human lymphocyte activation gene 3 is encoded by the LAG3 gene. When lag3 binds to MHC class II and other ligands, it sends inhibitory signals to T cells, which causes them to become dysfunctional.
Alpha-synuclein: Presynaptic neuronal protein α-synuclein is associated with Parkinson’s disease (PD) both neuropathologically and genetically.
Tau Protein: The central nervous system contains large amounts of tau protein. They are proteins linked to microtubules that support neuronal stability. They undergo hyperphosphorylation and self-assemble into paired helical filaments, which give rise to neurofibrillary tangles in Alzheimer’s disease.
Overall Evaluation:
Knowing the role of APLP1 and LAG3 interaction in producing the harmful proteins deepens insight into the molecular mechanisms of cell-to-cell transmission of pathologic alpha syn. Also provides therapeutic strategies aimed at preventing neurodegeneration in Parkinson’s disease and related alpha synucleinopathies.
Reference:
https://neurosciencenews.com/parkinsons-cancer-drug-26333/
Author : Alexandria Carolan
Source : Johns Hopkins Medicine