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The hypothesis of the gain of function in GCase theorizes that the mutant form of protein is recognized as misfolded, thus placing stress on mechanisms of protein degradation and interfering with α-synuclein breakdown and consequent endoplasmic reticulum stress, as observed in autophagy perturbations in cells derived from patients with GBA1 -associated PD (Fernandes et al., 2016)

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Perturbed or "anomalous" p K a values As has already been suggested, the intrinsic p K a values for ionizable groups are no guarantee that a particular residue in a particular protein will be in a particular ionization state at a pH consistent with its physiologically relevant structure and function