The population worldwide is aging, making widespread neurodegenerative diseases such as Alzheimer disease (AD), Parkinson disease (PD), Parkinsonian syndromes (Multiple System Atrophy and Progressive Supranuclear Palsy), and amyotrophic lateral sclerosis a real challenge for scientific research.
Although it is acknowledged that the etiology of neurodegenerative diseases is often multifactorial, particularly gene–environment interactions, the pathogenesis of many of these diseases is not fully understood (1). However, new research techniques, like Microscale Thermophoresis, have revealed the existence of fibrillar protein aggregates in some neurodegenerative diseases. This discovery provides valuable insights for future disease diagnosis and progression (2).
Common Neurodegenerative Diseases
The nervous system is a complex system of organs responsible for receiving and processing sensory information and is involved in the signaling and coordination of effector organs that form part of this complex network. Neurodegeneration describes the loss of neuronal structure and function in the nervous system. The neurological consequences of these pathologies can have devastating effects on the mental and physical functioning in patients (3).
Parkinson’s disease is a long-term degenerative disorder of the central nervous system that mainly affects the motor system (4). Symptoms like shaking, rigidity and slowness in movement, generally develop slowly over time (4). Some mental and behavioral problems have also been known to occur. For example, Dementia, depression and anxiety generally manifest in the advanced stages of the disease (5).
Alzheimer’s disease, is also a chronic neurodegenerative disease that usually starts slowly and worsens over time (6,7). It is the cause of 60% to 70% of cases of dementia worldwide. The most common early symptoms are difficulty remembering recent events (short-term memory loss) problems with language pronunciation, disorientation (including easily getting lost), mood swings, loss of motivation, and behavioural issues, which gradually appear with the progression of the disease (6,7).
The widespread progression of each of these neurodegenerative diseases is increasing the need for earlier diagnosis and better treatment. Until recently, though, research technology could not provide enough in-depth research into the inner workings of the diseases to give enough early warning at disease onset.
Disease Diagnosis Aided By MST’s Ability To Detect Small Molecules
Microscale Thermophoresis (MST) is a technique used to measure the interaction of biomolecules at an extremely detailed scale. The technology moves particles through a microscopic temperature gradient to measure any change in the structure of the molecule, which results in a relative change of movement along the temperature gradient. This relational change is used to determine binding affinities without the need of immobilization to a surface.
Fibrillar aggregation is a process that begins with the abnormal association of a few molecules. It has the potential to form larger structures called amyloids where many copies of the protein stick together forming fibrous deposits around cells, which can disrupt the healthy function of tissues and organs. This process could lead to the occurrence of neurodegenerative disorders and consequently, the progression of Alzheimer’s and Parkinson’s disease (8). Historically, identification of novel small compounds that bind fibrillar protein aggregates has proven difficult. In a study examining parallel complications to neurodegenerative disease pathology, MST was found to be an extremely useful tool to quantify interactions between small molecules and protein fibrillar aggregates. The results of the study also showed there is potential for practical applications of MST as a tool to be adapted for identification and development of therapeutic candidates of protein misfolding diseases.
MST is a powerful and practical methodology to quantify interactions between small molecules and protein fibrillar aggregates (8) that can be applied for early detection of protein misfolding diseases and allow physicians to treat the disease in the early stages of its progression.
- Rebecca C. Brown, Alan H. Lockwood, and Babasaheb R. Sonawane. Neurodegenerative Diseases: An Overview of Environmental Risk Factors. Environ Health Perspect. 2005 Sep; 113(9): 1250–1256. Published online 2005 May 26. doi: 10.1289/ehp.7567
- Fisher E, Zhao Y, Richardson R, Janik M, Buell AK, Aigbirhio FI, Tóth G. Detection and Characterization of Small Molecule Interactions with Fibrillar Protein Aggregates Using Microscale Thermophoresis. ACS Chem Neurosci. 2017 Jul 6. doi: 10.1021/acschemneuro.7b00228
- Cannon J. and Greenamyre J. The Role of Environmental Exposures in Neurodegeneration and Neurodegenerative Diseases. Toxicol Sci. 2011 Dec; 124(2): 225–250. Published Online 2011 Sep 13. doi: 10.1093/toxsci/kfr239
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- Dementia Fact sheet N°362. World Health Organization. Archived from the original on 18 March 2015. Retrieved 13 January 2016.
- Pulawski, W; Ghoshdastider, U; Andrisano, V; Filipek, S (2012). “Ubiquitous amyloids”. Applied Biochemistry and Biotechnology. 166 (7): 1626 -43. PMC 3324686 . PMID 22350870. doi:10.1007/s12010-012-9549-3