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Biomedical
Prompt Description
Create a figure illustrating the following experimental procedure: MCF7 cells were seeded and then subjected to five different cellular stressors: UV radiation, serum depletion, glucose starvation, DTT/PFA treatment, and hypoxia. This was done to stimulate the production of multivesicular bodies. Exosomes were then isolated via ultracentrifugation, stained with acridine orange, and analyzed via fluorescence microscopy.
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![A schematic diagram illustrating the impact of lactate on the CNS of AD patients. Lactate, a product of glycolysis, is an essential substrate for maintaining normal brain energy metabolism. Mitochondria, the "energy factories" in neurons, rely not only on glucose to produce ATP but also require astrocytes to provide "raw materials" such as lactate. Lactate produced by glycolysis in astrocytes can enter mitochondria for further oxidation, ultimately converting into CO2 and water. Astrocytes, the most abundant glial cells, play a crucial role in supporting neuronal energy demands. In the brain, lactate produced via glycolysis or stored glycogen (glycogenolysis) is released from astrocytes through monocarboxylate transporter 4 (MCT4). It is then absorbed by neurons via monocarboxylate transporter 2 (MCT2) on the neuronal membrane [34]. This lactate, after being converted to pyruvate, is oxidized by neuronal mitochondria. Thus, the described "astrocyte-neuron lactate shuttle hypothesis" is activated under aerobic conditions, where neuronal glutamatergic synaptic activity promotes lactate production in astrocytes, and astrocytes supplement the basal ATP production of neurons, typically derived from glucose carbon oxidation directly from neuronal glycolysis [35].
Under low glucose conditions, lactate glycogenolysis in astrocytes may be upregulated to meet neuronal demands. Lactate shuttling and carbon supply to neurons can be disrupted by various processes, including: downregulation of glucose transporters across the BBB leading to a general reduction in glucose uptake, decreased expression of hexokinase, and altered expression of astrocytic MCT4 and neuronal MCT2 during aging. In addition to this, the brain can also utilize lactate transported from other organs via the bloodstream. As early as the 1970s and 1980s, numerous researchers had already discovered that lactate could be "shuttled" between various groups.
In studies on improving cognitive dysfunction in AD patients, restoring mitochondrial function is considered a very effective approach. Current research has found that lactate is not only a "signaling molecule" but can also affect protein structure. In Lian et al.'s study on PD, it was found that SIRT1 can affect lactate homeostasis. They pointed out that excessive lactate accumulation in the brain can exacerbate the pathological features of PD, while deacetylation of pyruvate kinase M2 (PKM2) at K135 and K206 by SIRT1 to block its enzymatic activity, inhibiting glycolysis to reduce lactate production, alleviated PD [38]. SIRT1 also has a role in regulating mitochondrial dynamics. SIRT1 is a NAD+-dependent deacetylase mainly located in the nucleus, and elevated NAD levels in the body activate SIRT1 [39]. SIRT1 has been shown to improve mitochondrial oxidative metabolism and actively regulate autophagy and mitochondrial function under oxidative stress [40-42]. In some studies, SIRT1 has been shown to be involved in the clearance of Aβ and Tau proteins, and its deacetylation function has the following effects: first, the transcription factor](/_next/image?url=https%3A%2F%2Fpub-8c0ddfa5c0454d40822bc9944fe6f303.r2.dev%2Fai-drawings%2FcKA9jejJMp5uNe7lVgVtEuItcdsfIJvV%2F1a951d3f-b53e-440c-9f46-f23a03d0add4%2F2f94c1e2-dfcb-42c6-a2be-283de804b398.png&w=3840&q=75)
