Title:Molecular Pathology in Neurodegenerative Diseases
Volume: 13
Issue: 12
Author(s): Alexander H. Peden and James W. Ironside
Affiliation:
Keywords:
Neurodegeneration, proteinopathy, prion protein, Aβ protein, α synuclein, plaques, neurofibrillary tangles,
tau protein, molecular pathology, central nervous system (CNS).
Abstract: Neurodegenerative diseases are increasing in prevalence in many countries as the average age of their populations
increases, since many of these disorders occur more frequently in elderly individuals, placing an increasing burden
on healthcare resources. Most neurodegenerative disorders are associated with accumulations of abnormal proteins in the
central nervous system (CNS), which result in neuronal degeneration and ultimately neuronal death. Recent developments
in molecular pathology and genetics have allowed the identification of the abnormal proteins involved in many neurodegenerative
disorders and the genes that encode these proteins. This has led to a fuller understanding of the mechanisms of
many of these diseases, but this has not so far been accompanied by major improvements in diagnostic tests or treatments
for these disorders. Prion diseases are rare neurodegenerative disorders that are associated with the accumulation of a misfolded
host protein, the prion protein, in the CNS. Prion diseases have been considered as a paradigm for protein misfolding
diseases, but there are significant differences between prion diseases and other neurodegenerative disorders, not least
in the transmissible nature of prion diseases. In this review we give an overview of the wide range of neurodegenerative
diseases that affect humans, and compare the molecular pathology of prion diseases with other neurodegenerative diseases.
The concept of proteinopathy as a common mechanism in neurodegenerative disorders is explored, and we highlight
the improvements in diagnosis and management required to improve our treatment of these devastating conditions.
