Evidence for α-synuclein's Central Role in Parkinson's Disease

Parkinson's disease involves a greatly accelerated loss of vital dopamine-generating neurons in the brain, leading to the characteristic symptoms in earlier stages of the condition. In recent years, scientists have focused on the role of α-synuclein in the processes that cause this cell death:

The discovery of α-synuclein has had profound implications concerning our understanding of Parkinson's disease (PD) and other neurodegenerative disorders characterized by α-synuclein accumulation. In fact, as compared with pre-α-synuclein times, a "new" PD can now be described as a whole-body disease in which a progressive spreading of α-synuclein pathology underlies a wide spectrum of motor as well as nonmotor clinical manifestations.

At this point α-synuclein is taking on a similar role to beta-amyloid in Alzheimer's disease - a magnet for interest and research funds, while potential clinical intervention involves removing or other otherwise nullifying the buildup of this unwanted compound. Fairly compelling research results were recently published on this topic, wherein researchers managed to convincingly replicate the effects of Parkinson's in mice:

Misfolded protein transmits Parkinson's from cell to cell

A [team] injected a misfolded synthetic version of the protein α-synuclein into the brains of normal mice and saw the key characteristics of Parkinson's disease develop and progressively worsen. The study [suggests] that the disease is spread from one nerve cell to another by the malformed protein, rather than arising spontaneously in the cells.

Parkinson's disease has two distinct features: clumps of protein called Lewy bodies and a dramatic loss of nerve cells that produce the chemical messenger dopamine. When [the] team injected the misfolded α-synuclein into a part of the mouse brain rich in dopamine-producing cells, Lewy bodies began to form. This was followed by the death of dopamine neurons. Nerve cells that linked to those near the injection site also developed Lewy bodies, a sign that cell-to-cell transmission was taking place.

The study lends theoretical support to the handful of biotechnology companies that are sponsoring clinical trials of α-synuclein antibodies for Parkinson's ... At least one mystery still remains: why do the Lewy bodies appear in the first place? ... Parkinson's disease is not a disorder in which somebody injects synuclein into your brain. So what sets it in motion?

As is also the case for Alzheimer's it remains much debated as to how and why some people exhibit Parkinson's disease while others do not - which is not to say that there is any shortage of theories on how the condition progresses from its earliest stages. Just as for many other age-related conditions the commonplace correlations apply: being overweight and sedentary increases your risk, exercise and calorie restriction reduce it.

On the subject of Lewy bodies in Parkinson's disease, I noticed a couple of recently published papers suggesting that their appearance is symptomatic of a later stage of the condition, or less relevant to Parkinson's disease specifically - meaning that investigating their biochemistry may be less important than work on α-synuclein at this juncture:


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