A lack of zinc could be a contributing factor to Alzheimer’s and Parkinson’s diseases, according to researchers at the University of Wisconsin-Madison in the US.
Both diseases are associated with clumping of defective proteins in the brain and the researchers found that a shortage of zinc reduces protein stability and causes clumping. They also identified a protein that can combat protein clumping.
The researchers discovered a protein (Tsa1) in yeast cells, which chaperones and prevents other proteins from clumping together in conditions of low zinc (J. Biol. Chem., doi: 10.1074/jbc.M113.512384). Equivalent proteins exist in vertebrates (Prx1 and 2) and zinc deficiency could contribute to human diseases if the same process is at work in humans.
Zinc is vital for the correct folding of proteins; too much Zn kills cells but in low Zn conditions, incomplete proteins stick together. ‘This kind of protein [Tsa1] is important under conditions where you have a lot of unfolded or misfolded proteins. What it does is physically associate with these proteins and prevents them from interacting,’ explains Colin MacDiarmuid, lead author of the report. It also clears damaging reactive oxygen species.
When proteins lose their shape due to high temperature or chemical damage, they stop working and amalgamate. ‘Heat shock has been known for a long time to be a major stress in the environment and this [zinc deficiency] is something that causes the same thing as heat shock, the build-up of unfolded proteins,’ MacDiarmuid explains. When yeast cells were deprived of zinc, the number of chaperones spiked up to threefold. Excluding these chaperones led to protein clumps.
The Wisconsin group believes its findings could throw light protein on a range of protein aggregating diseases. ‘The obvious candidates are neurological conditions like Parkinson’s and prion disease, where you have these plaques of proteins that build up in the cell and essentially kill them,’ says MacDiarmuid.
However, neurobiologist Christian Holscher of the University of Lancaster, UK, commented that he doubts ‘that a low level of Zn is the reason why people develop Alzheimer’s or Parkinson’s disease. It might be one of many contributing factors at best.’
People with Alzheimer’s have amyloid aggregates in the brain, adds Holscher. ‘Ironically, the original suggestion was to reduce metal ions such as Zn, aluminium or copper, in order to reduce the aggregation of amyloid. A number of drugs have been developed over that last 10 years that try to reduce metal ion levels, but none of these have been successful.’
The World Health Organization estimates that more than 15% of the world’s population is at risk of zinc deficiency.