- A research team from multiple Universities including Cambridge
University has discovered that a steroid in a dogfish shark which protects
against Parkinson's disease.
- The synthesized steroid called squalamine was found to remove
toxic clumps of α-synuclein
- This could aid in the treatment of Parkinson's and other
similar neurodegenerative diseases.
steroid made by the dogfish shark was synthesized artificially, by a
multi-University research team including Cambridge University, and which was found
to prevent the buildup of a protein associated with neurodegenerative diseases
. The lethal protein called
alpha-synuclein (α-synuclein) could be a potential target of drug therapy for
such neurodegenerative diseases. The
newly synthesized steroid was called squalamine and it was found to reduce the
α-synuclein clumps that are found in patients with Parkinson's disease.
Functions of Squalamine
findings of the study show that squalamine
- prevents the build up of α-synuclein
- eliminates it from the neurons by removing the protein which
clings to the the inner wall of nerve cells.
study was conducted on genetically engineered nematode worm C. elegans
, altered to produce human
α-synuclein in its muscles. When the worms grow in age, the build up of
α-synuclein inside the muscle cells leads to cellular damage and paralysis.
‘Squalamine from dogfish shark could be a potentially effective therapy for Parkinsonís and other neurodegenerative diseases.’
Michael Zasloff who is the co-senior author of the study and a professor at
George Town University said that the researchers found that when squalamine was
administered orally to the worms, it prevented the clustering of α-synuclein
and limited muscular paralysis within the worms.
1993, Dr. Zasloff† discovered the
protein in dogfish sharks and in 1995 he synthesized Squalamine. The process
that is used to synthesize squalamine does not include the use of any shark
tissue. Since then, there have been numerous research conducted on the benefits
of using squalamine, with many researchers identifying anticancer as well as
anti-viral properties of the protein. This study on the neurological benefits
in diseases like Parkinson's is the first of its kind.
function of the protein α-synuclein in the healthy brain is unknown but this
protein is of great interest to Parkinson's researchers. It is a constituent of
Lewy bodies, or protein clumps which are considered the pathological hallmark
for Parkinson's disease.
pathology of alpha-synuclein pathology exists in parts of the brain that are
not traditionally related to Parkinson's disease, as it is also found in
patients who have no clinical features of Parkinson's. This has fueled many
research studies to identify the emerging hypothesis that the disease may
affect many areas beyond the substantia nigra in the central nervous system.
The diversity of the clinical features associated with Parkinsons has renewed
interest in studying about α-synuclein. There are research projects that are
aimed at identifying if α-synuclein has potential use as a biomarker of
are currently being developed to target alpha-synuclein in Parkinson's
patients. These vaccines are only in the initial stages of a clinical trial.
Squalamine in Parkinson's Disease
were a series of in vitro experiments to understand the effect of squalamine on
the levels of α-synuclein. It was found that
- squalamine was positively charged with increased affinity
towards negatively charged membranes that resulted in the α-synuclein
being completely removed from membranes that are negatively charged.
- squalamine protected the neuronal cells that were healthy by
preventing them from getting attached to masses of α-synuclein.
- Oral administration of squalamine was carried out on C. elegans
with Parkinson's disease. This was found to prevent the toxic α-synuclein
clumps from forming.
- The loss of mobility that occurred due to the accumulation of
toxic α-synuclein was prevented.
study was not only successful in the invitro studies but was also found to be
successful in the animal studies.
on the abundant abnormal α-synuclein pathology†
are gaining in importance as they characterize neuropathological
disorders that not only includes Parkinson's Disease patients but also patients
with other neurodegenerative diseases which are collectively called
"synucleinopathies." Various models have been structured to identify the role
played by this protein in the pathogenesis of these diseases, identifying
pathway ad deciphering the consequences of their accumulation.
Squalamine in Sharks
have developed mechanisms that help defend themselves from environmental
microbes in order to survive. There are multiple mechanisms that include
humoral as well as cellular responses.
are a number of low molecular weight antibiotics that have been discovered over
the past few years and which are believed to play an important role in the
defense against environmental microbes. The identified molecules include
lipids, peptides and alkaloids. In the course of discovery, scientists found
that the stomach extracts of Squalus acanthias, a shark, was found to exhibit
potent antimicrobial activity.
discovery of squalamine in removing the toxic clumps of α-synuclein could
herald in a better method of treatment of Parkinson's and other associated
neurodegenerative diseases. This synthesized protein could be an effective
therapy for the disease and aid in better care for Parkinson's disease
- Squalamine:An aminosterol antibiotic from the shark - (https://www.michaeljfox.org/understanding-parkinsons/living-with-pd/topic.php?alpha-synuclein)
- α-Synuclein in Parkinson's Disease - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC45871/pdf/pnas01102-0225.pdf)
- Alpha-synuclein and Parkinson's Disease - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281589/)