Allergies to fish are not common, but when they do occur they are most often caused by the fish protein β-parvalbumin, which is found in many different fish species. New research by a team at Chalmers University of Technology in Sweden now suggests that this same abundant protein may have a protective effect against Parkinson’s disease (PD). In vitro studies led by Pernilla Wittung-Stafshede, Ph.D., professor and head of the chemical biology division at Chalmers, showed that β-parvalbumin found in Atlantic cod effectively prevents the human protein α-synuclein (αS) from aggregating into the toxic amyloid fibrils in the brain that are characteristic of PD. The results found that fish β-parvalbumin amyloids that form in the human gut effectively scavenge and bind the human αS proteins, which inhibits subsequent αS amyloid formation.
The findings are particularly interesting because, as the researchers write in their published paper in Scientific Reports, PD may have its origins in the gut. “It is not clear where PD starts but it is proposed that it may originate from the gut via the enteric nerve system.…Of importance for initiation and spreading of PD, it was shown recently that αS is expressed in enteroendocrine cells of the gut epithelium; these cells directly connect to αS-containing nerves and thus form a neural circuit from the gut to the brain.”
Reporting on their research in Scientific Reports, the authors conclude that while the findings will need to be confirmed through multiple in vivo studies, “we speculate that eating PV-rich fish is a dietary recommendation that may prevent or delay PD.” Their paper is entitled “Abundant Fish Protein Inhibits α-Synuclein Amyloid Formation.”
A number of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease, are characterized by the self-assembly of native proteins into amyloid fibers. In PD, which is the second most common neurodegenerative disorder behind Alzheimer’s disease, conformational changes in the intrinsically unstructured αS protein cause it to assemble into amyloid fibers that are toxic and can be transmitted from cell to cell.
A fish-rich diet is widely considered to be beneficial against age-related disorders, including cardiovascular disease and dementias. “Among those who follow a Mediterranean diet, with more fish, one sees lower rates of Parkinson's and Alzheimer's,” says co-lead researcher Tony Werner, in the department of biology andbiological engineering. Omega-3 and omega-6 fatty acids in fish are assumed to be responsible for the health benefits of fish, but as the Chalmers University of Technology team points out, “direct evidence is lacking, and thus other fish components may as well be responsible.”
Most fish are rich in proteins known as β-parvalbumins, which are also the major allergen in people who do have fish allergies. Recent research suggests that food allergans, including β-parvalbumins, can form amyloid structures that survive transit through the harsh conditions of the gastrointestinal tract. “This phenomenon has been reported for allergenic proteins in various food, such as β-lactoglobulin, caseins, ovalbumin, lysozyme, and β-parvalbumin,” the team writes.
Research has also shown that human amyloidogenic proteins can cross-react, and so the Chalmers University team reasoned that fish β-parvalbumin might have the ability to interact with human amyloidogenic proteins, such as αS. The team carried out a series of in vitro biophysical studies to test out their hypothesis and investigate any cross-talk between Atlantic cod β-parvalbumins and human αS.
Their results showed that β-parvalbumins inhibit the formation of αS amyloid fibrils via a mechanism that involves binding of the αS monomers to β-parvalbumin amyloids. “We determined that PV amyloids inhibit αS amyloid formation by scavenging αS monomers to the PV amyloid fiber surface, possibly by interactions with protruding Ca-binding loops,” the authors write. “Parvalbumin collects up the 'Parkinson's protein' and actually prevents it from aggregating, simply by aggregating itself first,” comments Dr. Wittung-Stafshede.The team notes that the binding of one amyloidogenic protein to the surface of preformed amyloids of another protein and its action as an inhibitory mechanism haven't been described before.
Herring, cod, carp, sockeye salmon, and red snapper are particularly high in β-parvalbumin, although the protein is abundant in many other fish species. Interestingly, levels of β-parvalbumin can vary throughout the year. “Fish is normally a lot more nutritious at the end of the summer, because of increased metabolic activity. Levels of parvalbumin are much higher in fish after they have had a lot of sun, so it could be worthwhile increasing consumption during autumn,” says co-author Nathalie Scheers, Ph.D., an assistant professor in the department of biology and biological engineering. Dr. Scheers’ previous research had looked at β-parvalbumin as a marker of fish consumption in human diets. “This protein has been evaluated as a compliance marker for fish intake in human diet interventions and epidemiological studies since humans express mostly another isoform, α-parvalbumin,” the researchers explain.
The Chalmers University of Technology is keen to study whether their findings could have implications for neurodegenerative disorders other than PD that are characterized by amyloid formation. “These diseases come with age, and people are living longer and longer,” Dr. Wittung-Stafshede notes. “There's going to be an explosion of these diseases in the future—and the scary part is that we currently have no cures. So we need to follow up on anything that looks promising.”
