A team at Osaka University in Japan has added a new piece to the puzzle of Parkinson’s disease. Their research points to misfolding of the alpha-synuclein protein as a potential driver of how the illness begins and progresses. The findings, reported in the Proceedings of the National Academy of Sciences, contribute to a growing effort to map the earliest cellular changes that lead to the visible symptoms of Parkinson’s and tracking their evolution over time.
Parkinson’s disease is a neurodegenerative condition that gradually affects the central nervous system. Early on, individuals may notice slower movement, tremor, and challenges with coordination. As the disease advances, brain cells sustain increasing damage, and overall motor function declines. The condition is defined by a sequence of neuronal losses that unfold at varying rates from person to person.
In Parkinson’s, an excess buildup of the alpha-synuclein protein occurs inside brain cells. This accumulation forms abnormal structures known as Lewy bodies, which are linked to the death of neurons in a brain area called the substantia nigra. The loss of these neurons is thought to contribute to both motor symptoms and a range of non-motor features that accompany the disease.
The Osaka study reveals that the disease-associated alpha-synuclein is not present in its normal form in affected individuals. Instead, it becomes misfolded, changing how it behaves inside cells. Normally, misfolded proteins are handled by lysosomes, the cell’s waste-disposal system, which digests unwanted material. In some cases, however, the altered alpha-synuclein evades this cleanup and escapes into other cellular compartments.
When lysosomes fail or rupture and can no longer contain the misfolded protein, the abnormal alpha-synuclein can spread to neighboring cells. This intercellular movement could propagate damage, heightening cellular stress and spreading the misfolded protein across tissues. As this load grows, it may further disrupt lysosomes, creating a cycle that speeds up degeneration.
Researchers propose that a specific misfolding pattern of alpha-synuclein might trigger neuronal degeneration and contribute to Parkinson’s as well as certain forms of Alzheimer’s disease. Yet the exact routes by which misfolded alpha-synuclein travels within the brain and body remain under investigation, with scientists aiming to chart the full sequence from early misfolding to clinical symptoms.
Although some familial forms of Parkinson’s have a genetic basis, not all cases are inherited. The new insights about alpha-synuclein misfolding add another layer to the broader effort to understand how genetic, environmental, and cellular factors come together to produce the disease. Ongoing research across laboratories worldwide seeks to translate these discoveries into therapies that intervene early in the disease process, with the aim of slowing or halting progression.
The study highlights the central role of protein misfolding in neurodegenerative disease and points to the need for continued exploration of how misfolded alpha-synuclein moves and damages brain cells. By deepening knowledge of these mechanisms, researchers hope to identify biomarkers for early detection and develop treatments that shield neurons from the stress caused by misfolded protein. Such progress could yield meaningful benefits for patients in Canada, the United States, and beyond.