Parkinson’s disease: Blocking brain enzyme corrects motor symptoms in mice

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  • Parkinson’s disease and symptoms:

Parkinson’s disease is a movement disorder that results due to loss of dopamine -producing cells in the brain. It has four main symptoms: 1. Tremor 2. Rigidity 3. Slowness of movement. 4. Impaired balance and coordination.

Other symptoms may be:

  • Depression and emotional changes
  • Difficulty speaking, chewing, swallowing
  • Constipation or urinary problems
  • Skin Problems
  • Disturbed sleep

As the disease progresses, patients may struggle to walk, talk and carry out normal life. Usually happens at the age of 60, progressing at different speeds in different people.

  • Causative Agent:

Although the exact trigger is not known, scientists suspect that clumps of faulty protein called alpha-synuclein that damages brain cells is involved. This is a key research area for Dr. Myöhänen, who leads a group investigating the role of PREP in neurodegenerative disorders. In the new study, the team experiments with a compound called KYP-2047 that blocks PREP in a mouse model of Parkinson’s.

  • PREP blocker also enhances dopamine production

The results show that the PREP blocker clears the animal’s brains of alpha synuclein aggregates and corrects the motor symptoms that are characteristic of parkinsonism.

  • Research project:

The mice were first treated with a virus that altered their genes so that their brains produced large amounts of alpha-synuclein. As they aged, their brains started to accumulate misfolded protein and they developed the motor symptoms.

The team started treatment with PREP blocker only after the animals started to show clear motor dysfunction. This would be like treating patients who are typically diagnosed with movement impairment. The researchers were surprised to see the rapid improvement made by mice. In their paper, they note:

“Following 4 weeks of PREP inhibition, we saw an improved spontaneous forelimb use in mice that correlated with a decreased immunoreactivity against oligomer-specific forms of aSyn [alpha-synuclein].”