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Doppel (PRND): The Enigmatic Prion Protein Paralog in Development and Disease

Endocrinology Diagnostics

Key points about Doppel (PRND):

Structure:

  • Prion protein paralog
  • Three α-helices, two-stranded β-sheet
  • Lacks octapeptide repeat region
  • Downstream of PRNP gene

Expression:

  • Primarily in testis
  • Limited during normal growth
  • Highest in spermatids and mature sperm

Reproductive Role:

  • Critical for sperm development
  • Aids acrosome formation
  • Influences sperm motility
  • Controls calcium levels

Molecular Characteristics:

  • GPI anchor attachment
  • More stable protein fold
  • Ancient gene duplication (500 million years ago)

Neurological Implications:

  • Normally absent from nervous system
  • Abnormal brain presence linked to neurotoxicity
  • Can cause cerebellar degeneration

Pathological Potential:

  • Associated with neurological disorders
  • Disrupts neuronal calcium balance
  • Possible target for neurodegenerative disease research
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