The role of chaperones and co-chaperones in α-synuclein metabolism and pathology. As a general concept, chaperones mediate several cellular strategies that maintain protein homeostasis. In synucleinopathies, misfolded α-synuclein can be refolded, degraded, secreted or sequestered into mature aggregates such as Lewy bodies. Direct stabilization and refolding, degradation via different protein degradation pathways and sequestration into aggregates are mechanisms that are assisted or modulated by chaperones and co-chaperones. Failure of these mechanisms abolishes protein homeostasis and thus promotes α-synuclein accumulation, oligomer formation, toxicity and potentially cell-to-cell propagation of α-synuclein pathology.