sodium-lactate and Parkinson-Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder induced by the loss of dopaminergic neurons in midbrain. The mechanism of neurodegeneration is associated with aggregation of misfolded proteins, oxidative stress, and mitochondrial dysfunction. Considering this, the process of removal of unwanted organelles or proteins by autophagy is vitally important in neurons, and activation of these processes could be protective in PD. Short-time acidification of the cytosol can activate mitophagy and autophagy. Here, we used sodium pyruvate and sodium lactate to induce changes in intracellular pH in human fibroblasts with PD mutations (Pink1, Pink1/Park2, α-synuclein triplication, A53T). We have found that both lactate and pyruvate in millimolar concentrations can induce a short-time acidification of the cytosol in these cells. This induced activation of mitophagy and autophagy in control and PD fibroblasts and protected against cell death. Importantly, application of lactate to acute brain slices of WT and Pink1 KO mice also induced a reduction of pH in neurons and astrocytes that increased the level of mitophagy. Thus, acidification of the cytosol by compounds, which play an important role in cell metabolism, can also activate mitophagy and autophagy and protect cells in the familial form of PD.

Topics: alpha-Synuclein; Animals; Astrocytes; Autophagy; Cytoprotection; Dopaminergic Neurons; Fibroblasts; Humans; Hydrogen-Ion Concentration; Mice; Mice, Knockout; Mitochondria; Mitophagy; Oxidative Stress; Parkinson Disease; Protein Kinases; Pyruvic Acid; Sodium Lactate; Ubiquitin-Protein Ligases

Monoamine oxidase type B (MAO-B) activity is elevated in certain neurological diseases such as Alzheimer's and Parkinson's disease with respect to age-matched controls; the cause of this elevation is unknown. The documented accumulation of aluminum in certain neurodegenerative diseases prompted us to test the effect of Al3+ on the activity of MAO-B in rat brain homogenate. Results showed that the metal ion significantly increased MAO-B enzymatic activity in a dose-dependent manner, yielding a K(M) of 5.69 microM compared with 34.45 microM in the absence of the metal ion. The Vmax of 45.34 micromol/min was unchanged in the presence of the metal ion.

Topics: Aluminum; Aluminum Compounds; Alzheimer Disease; Animals; Brain; Cell Extracts; Deamination; Dose-Response Relationship, Drug; Enzyme Activation; Kinetics; Lactates; Male; Monoamine Oxidase; Parkinson Disease; Phenethylamines; Rats; Rats, Wistar; Sodium Lactate; Thermodynamics