Minocycline as a potential therapeutic agent in neurodegenerative disorders characterised by protein misfolding

Abstract

Many neurodegenerative disorders share common features including the accumulation of aggregated misfolded proteins, neuroinflammation and the induction of apoptosis. While the contributions of each of these individual elements to neuronal death remain unclear, a commonly used antibiotic, minocycline, has been shown to reduce the progression and severity of disease in several models of neurodegeneration by variously downregulating these molecular pathways. Here we discuss the evidence for the potential of minocycline as a broad-specificity therapeutic agent for those neurodegenerative diseases that are characterized by the presence of misfolded proteins.

Figure 1

The chemical structure of minocycline and tetracycline. Figure shows the common core of 4x six-membered rings. Modifications at three sites on the conserved tetracycline structure on minocycline are indicated in red.

Figure 2

Summary of some of the molecular pathways targeted by minocycline that are common to many neurodegenerative disorders. Common disease-associated events known to be targeted by minocycline include (1) neuroinflammation with the release of pro-inflammatory mediators, (2) apoptosis, caspase activation and caspase-mediated protein proteolysis and (3) protein misfolding and aggregation. Abbreviations: inducible nitrogen oxide synthase (iNOS); matrix metaloproteases (MMP); cyclooxygenase-2 (COX-2).