Neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). All of these diseases are characterized and defined by the accumulation of protein aggregates in the brain. Studies have recently described the ability of these disease-associated protein aggregates to traffic between cells, resulting in amplification and propagation of their disease-causing pathology.
Parkinson’s disease is caused by a loss of nerve cells in the part of the brain called the substantia nigra. Nerve cells in this part of the brain are responsible for producing a chemical called dopamine. There have been several notable celebrities that have been diagnosed with Parkinson’s disease such as Micheal J. Fox, George H.W. Bush, and Muhammed Ali. According to the National Institute of Neurological Disorder and Stroke, they claim that approximately 500,000 Americans are diagnosed with Parkison’s disease, but given that many individuals go undiagnosed or are misdiagnosed, the actual number is likely much higher. Some experts estimate that as many as 1,000,000 Americans have Parkinson's disease as of June 2022.
In “Endocytic Vesicle Rupture is a Conserved Mechanism of Cellular Invasion of Amyloid Proteins'', by William Flavin et al, the amyloid assemblies and their ability in rupturing intracellular vesicles after endocytosis along with their association to these neurodegenerative diseases are being studied. Flavin et al. examined patients' brains that had Parkinson's disease in slices and were able to conclude that vesicle rupture could be induced by α-synuclein assemblies. Their research gave a better understanding of how amyloid proteins were capable of causing cellular dysfunction. Flavin et al.’s research demonstrated some of the biological mechanisms that come into play along with neurological diseases.
In a study just published in the journal Nature Structural and Molecular Biology, researchers presented 76 proteins that might serve as biomarkers for the detection of Parkinson's disease. This study is quite noteworthy and special as while the potential biomarker proteins are found in both healthy and diseased individuals, their molecules are present in different shapes (or structures) in each of the two groups. Again, it is not the presence of certain proteins that indicates the disease, but rather the shape they have assumed. This is the first time that scientists have shown that an analysis of the structures of all proteins in a body fluid can identify potential biomarkers for disease. From what has been seen so far, they're actually a very strong indicator for the disease according to the study. Natalie de Souza, senior scientist in Paola Picotti's group and one of the study's co-authors, is confident that this idea of structural biomarkers will “bear out”.
While there is still more research to be done about neurodegenerative diseases such as Parkison’s disease, we can use the idea of the structure of the proteins in Flavin’s research and contemplate how their respected mechanisms work together. However, the research stating that Parkisons could be identified by the shape of the proteins is quite promising in terms of diagnosing patients. Thus, both of these studies have given a better understanding of the biological mechanisms that come into play with neurodegenerative diseases such as Parkinson’s disease.
References:
ETH Zurich. "Protein shapes indicate Parkinson's disease." ScienceDaily. ScienceDaily, 28 November 2022. <www.sciencedaily.com/releases/2022/11/221128101246.htm>.
Flavin, William P et al. “Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.” Acta neuropathologica vol. 134,4 (2017): 629-653. doi:10.1007/s00401-017-1722-x
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