Emerging drugs and advances for the treatment of neurodegenerative conditions:
3rd year MBBS, Goa Medical College
An octopus has the largest brain-to-body ratio of any invertebrate and nearly the same number of neurons as a dog, so it was no big surprise when the salivary glands of an octopus yielded a molecule with significant neurological impact—octopamine.
Octopamine is the fight-or-flight neurotransmitter in invertebrates and is found in trace amounts in humans. A recent study found that when octopamine is introduced into a culture of astrocytes in small amounts, it causes the production of lactate. The lactate can then be broken down by cells that are on the verge of cell death due to ATP depletion to release energy. α-synuclein is a protein that is responsible for plenty of neurodegenerative diseases called synucleinopathies (ex-Parkinson’s). Accumulation of this protein results in pathological changes leading to motor and cognitive impairment. A hallmark of synucleinopathies is astrocytosis.
The scientists discovered that the protein calcineurin, which generally regulates Ca2+ metabolism, played a significant role in astrocytosis. Astrocytes are the most numerous glial cells in the central nervous system. Reducing the levels of calcineurin prevented the conversion of astrocytes from neuroprotective to neurotoxic. In neurons undergoing -synuclein proteotoxic stress, reducing calcineurin caused a release of octopamine.
The scientist described the functioning of octopamine in the brain as being like that of an SOS signal. Neurons that are stressed send the signal, which is read by astrocytes. Octopamine allows astrocytes to read this stress signal and start making energy that will protect the cells from death due to a lack of ATP.
Determining its protective role against α-synuclein mediated neural degeneration could pave the way for revolutionary new treatments for various neurodegenerative disorders.
Pathological alterations in octopamine levels have been found not only in α-synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies but also in psychiatric diseases such as schizophrenia and bipolar disorder, proving just how wide the scope of this discovery is.
Source: “Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein” by Andrew Shum et al. PNAS
Julia Carney said, “Little drops of water make a mighty ocean”. But in the case of the scientists at the University of Minnesota, nanoparticles opened up an ocean of opportunity.
Misfolded proteins, an indication of various neurodegenerative disorders, can accumulate in tissues and can sometimes even be detected in the circulation years before the onset of clinical symptoms. Real-time quaking-induced conversion (RT-QuIC), a protein-based seeded amplification assay, can be used to detect these proteins. It is found to be more than 80% accurate for the correct diagnosis of Creutzfeldt-Jakob disease by detecting the prions, and it is used for plenty of other protein detections. But a major drawback is that it takes about 14 hours to perform this test, making it hard to use in a clinical setting.
Interestingly, when 50-nm silica nanoparticles were added to RT-QuIC assay experiments, huge performance improvements were seen. Named Nano-QuIC, it was now 10 times more sensitive and took only 4 hours—easily 10 hours less! Moreover, no false positives were reported, showing increased reliability.
The study mainly focused on chronic wasting disease in deer, but the researchers believe that this technology can have a strong impact on the diagnosis of neurodegenerative diseases in the near future. A nanostep for man, a giant leap for mankind
3rd year MBBS
Goa Medical College, Goa
Source: “Nanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded ProteinsNanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded Proteins” by Sang-Hyun Oh et al. Nano Letters