Graphic illustration of a neuron, Ethan Hein
The scientists have experimented with low doses of the antibiotic drug doxycycline. The antibiotic appears to reduce the toxicity of a protein called (alpha) α-synuclein. Interestingly, the investigation into the beneficial effects of doxycycline cam about serendipitously five years ago. Here, Dr. Marcio Lazzarini, who was working at the Max Planck Institute of Experimental Medicine, undertook experiments in mice to find new treatments for Parkinson’s using a neurotoxin.
Neurotoxins are toxins that are poisonous or destructive to nerve tissue (causing neurotoxicity). Neurotoxins inhibit neuron control over ion concentrations across the cell membrane, or communication between neurons across a synapse.
Parkinson’s disease is a degenerative disorder of the central nervous system. It is triggered by alpha-synuclein aggregates. These protein formations lead to loss of dopamine-generating cells. Symptoms of the disease include hand shaking or difficulty walking. With Parkinson’s disease brain cells exhaust themselves, like engine motors burning themselves out, and die prematurely. The cells die because they generate and accumulate too many waste products. This explains why the disease affects some regions of the brain and not others.
The effects of Parkinson’s disease - tremors, stiffness and slow voluntary movements – are due to the destruction of dopaminergic neurons. The Brazilian researchers are of the opinion the cells become damaged when, subject to special conditions, small aggregates of α-synuclein accumulate.
Magnetic Resonance Imaging (MRI) scans of the brains of prisoners diagnosed with psychopathy showed reduced connectivity between an area of prefrontal cortex (red) and the amygdala (blue) through the white matter connecting the two (green).
University of Wisconsin-Madison
Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's occur as a result of neurodegenerative processes.
When carrying out mouse models to examine Parkinson’s disease, Dr. Lazzarini, gave the mice a neurotoxin termed 6-hydroxydopamine (6-OHDA). This toxin causes the death of dopaminergic neurons. The effect of this is to produce an effect similar to Parkinson’s disease.
On one occasion, as Bioscience Technology reports, when 40 mice were given the neurotoxin, only two of the mice went onto develop the Parkinson’s-like symptoms. The other mice appeared to be healthy. Investigating this seemingly anomalous result, the scientist found that the mice had accidently been fed food containing the antibiotic doxycycline.
This led to the hypothesis that doxycycline could offer a protective effect against Parkinson’s disease, by protecting the neurons. To demonstrate this, the researchers ran the study again. This time the mice were given the antibiotic in low doses via peritoneal injection. The effects were similar – this time none of the mice showed Parkinson’s disease symptoms.
The next phase of the research was to use structural and spectroscopic characterization methods to study why this neuroprotective effect occurs. These methods are: infrared spectroscopy, nuclear magnetic resonance, and X-ray scattering.
By applying these methods, the researchers observed when cells are placed in a medium without the antibiotic; the protein aggregates and amyloid fibrils began forms. However, in a second medium, containing doxycycline the α-synuclein created a different type of aggregate which had a different shape and size. This difference in shape could explain why Parkinson’s disease symptoms might occur.
Further analysis showed how showed how the presence of doxycycline in a medium reduces α-synuclein aggregation by over 80 percent. This was found using human neuroblastoma cells. Further studies will be conducted using both human cells and mouse models. These tests may confirm whether doxycycline alters the expression of key genes for the development of Parkinson’s disease.
The research has been published in the journal Scientific Reports. The research is titled “Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species.”
In related news, medical scientists are developing a simple breath test to detect and diagnose Parkinson’s disease at an early stage. This is based on screening for certain volatile organic compounds when a person exhales.