ABSTRACT
The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Subject(s)
Humans , Prions , Neurodegenerative Diseases/pathology , Amyloid beta-Peptides , Alzheimer Disease , alpha-Synuclein , tau Proteins , Parkinson DiseaseABSTRACT
A method for the rapid enantioseparation of five β-blocker drugs, including alprenolol, propranolol), mexiletine, metoprolol and pindolol was developed by a 5-cm short column packed with perphenylcarbamoylated β-cyclodextrin(CD) chiral stationary phase by HPLC. The results showed that except for alprenolol), the other 4 β-blocker drugs were completely separated using ACN-0.1% thriethylammonium acetate(TEAA), 40∶ 60, V/V, pH=4.0) as mobile phase. The 5-cm short CD-based column exhibited rapid separation ability to the above β-blocker drugs within 5 min, which indicated that the separation has high efficiency. According to the chemical structures of the β-blockers and their chromatographic behavior, related separation mechanisms were also discussed. The proposed method was rapid, effective and repeated.