Science: New Study Reveals the Mechanism of The Extensive Neuronal Loss in Alzheimer's Disease
This new research was published in the Science journal on September 15, 2023. It reveals the potential key factors behind neuronal loss in Alzheimer's disease, namely, an RNA gene called MEG3 and this process of necroptosis. These findings mark an important step toward further understanding the fundamental mechanisms of this complex.
A New Model for Unraveling the Alzheimer's Mystery
Most mouse models used in research couldn't naturally replicate these features, leaving scientists with questions about the relationship between these features and the progression of the disease.
To address this limitation, the researchers constructed a new model by implanting both healthy human neurons and mouse neurons into the brains of Alzheimer's disease mouse models simultaneously. The degeneration of these human neurons in the mouse brain closely resembled their counterparts in the human brain, enabling us to study them during the brain aging process and gain new insights into the basic processes of Alzheimer's disease.
It was observed that Alzheimer's disease characteristics, such as tau tangles and substantial neuronal loss, were only evident in human neurons and not in rodent neurons, mirroring the conditions observed in patients. This suggests that Alzheimer's disease may involve human-specific factors that standard mouse models cannot replicate.
The Culprit Behind Neuronal Loss
Using this new model, the authors delved deeper to discover the reasons behind neuronal death in Alzheimer's disease. They made a crucial breakthrough: in this model, they activated a pathway called necroptosis, leading to neuronal death, where necroptosis is a programmed cell death process.
Fig.2 Neurons immunoreactive to AT8, PHF1 or MC1. (Balusu, 2023)
Furthermore, they found that in human neurons, a molecule called MEG3 significantly increased, which was also observed in Alzheimer's disease patients.
They also found that by reducing MEG3 and preventing necroptosis, they could, in turn, prevent cell death. More research is needed to understand how exactly MEG3 triggers necroptosis, but this finding represents a significant step forward in understanding how Alzheimer's disease leads to the loss of brain neurons.
Necroptosis has become an active area of drug development for conditions like cancer and amyotrophic lateral sclerosis (ALS). While there is still much to explore, these findings open a hopeful path for potential therapies for Alzheimer's disease and also offer promise for traditional treatments targeting amyloid and tau.
More information: Balusu, Sriram, et al. "MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer's disease." Science 381.6663 (2023): 1176-1182.
- iNeuMab™ Anti-FGFR1 Antibody (NRP-0422-P1244) (Cat#: NRP-0422-P1244)
- iNeuMab™ Rabbit Anti-LRRK2 Monoclonal Antibody (CBP1887) (Cat#: NAB-08-PZ735)
- iNeuMab™ Anti-SEZ6 Antibody (NRP-0422-P517) (Cat#: NRP-0422-P517)
- Mouse Anti-Human α-Synuclein Phospho (Tyr39) (CBP3706) (Cat#: NAB201250LS)
- iNeuMab™ Rabbit Anti-Alpha-synuclein (CBP1631) (Cat#: NAB-08-PZ079)
- iNeuMab™ Anti-F-Spondin/SPON1 Antibody, Clone 3F4 (Cat#: NRZP-0822-ZP4740)
- iNeuMab™ Anti-GD2 Antibody (NRZP-1222-ZP767) (Cat#: NRZP-1222-ZP767)
- iNeuMab™ Anti-Tau Antibody (NRP-0422-P1760) (Cat#: NRP-0422-P1760)
- iNeuMab™ Anti-ApoC3 BBB Shuttle Antibody (NRZP-1022-ZP3503) (Cat#: NRZP-1022-ZP3503)
- iNeuMab™ Anti-ApoC3 BBB Shuttle Antibody (NRZP-1022-ZP3505) (Cat#: NRZP-1022-ZP3505)
- Human Astrocytes, Immortalized (Cat#: NCL-2105-P182-AM)
- Rat Schwann Cells RSC96, Immortalized (Cat#: NCL-2108P21)
- Mouse Microglia from C57BL/6 (Cat#: NCL-21P6-082)
- Mouse Midbrain Dopaminergic Neuron Cell MN9D (Cat#: NCL2110P059)
- iNeu™ Human Motor Neurons (Cat#: NCL-2103-P71)
- iNeu™ Human Schwann Cell (Cat#: NCL-2103-P63)
- Human Dental Pulp Stem Cells (Cat#: NRZP-1122-ZP113)
- Rat Olfactory Ensheathing Cells (Cat#: NRZP-1122-ZP162)
- Human Brain Vascular Adventitial Fibroblasts (Cat#: NCL-21P6-014)
- Human Blood Brain Barrier Model (Cat#: NCL-2103-P187)
- Amyloid beta 1-42 Kit (Cat#: NRP-0322-P2170)
- Human GFAP ELISA Kit [Colorimetric] (Cat#: NPP2011ZP383)
- Human Poly ADP ribose polymerase,PARP Assay Kit (Cat#: NRZP-1122-ZP62)
- Beta Amyloid (1-40), Aggregation Kit (Cat#: NRZP-0323-ZP199)
- Human Tau Aggregation Kit (Cat#: NRP-0322-P2173)
- Beta Amyloid (1-42), Aggregation Kit (Cat#: NRZP-0323-ZP200)
- Alpha Synuclein Aggregation Kit (Cat#: NRZP-1122-ZP15)
- Alpha-Synuclein Aggregation Assay Kit (Cat#: NRZP-1122-ZP37)
- Dextran, NHS Activated (Cat#: NRZP-0722-ZP124)
- VSV-eGFP (Cat#: NTA-2011-ZP20)
- AAV2 Full Capsids, Reference Standards (Cat#: NTC2101070CR)
- App Rat amyloid beta (A4) precursor protein (App)(NM_019288) ORF clone, Untagged (Cat#: NEP-0421-R0053)
- Human huntingtin (HTT) (NM_002111) ORF clone, Myc-DDK Tagged (Cat#: NEP-0521-R0497)
- Lenti of Human TAR DNA binding protein (TARDBP) (NM_007375) ORF clone, mGFP Tagged (Cat#: NEP-0521-R0832)
- Mouse Parkinson disease (autosomal recessive, early onset) 7 (Park7) (NM_020569) clone, Untagged (Cat#: NEP-0621-R0133)
- Rat Parkinson disease (autosomal recessive, juvenile) 2, parkin (Park2) (NM_020093) ORF clone/lentiviral particle, Myc-DDK Tagged (Cat#: NEP-0621-R0041)
- Lenti of Mouse synuclein, alpha (Snca) transcript variant (NM_001042451) ORF clone, mGFP Tagged (Cat#: NEP-0521-R0864)
- Mouse SOD1 shRNA Silencing Adenovirus (Cat#: NV-2106-P14)
- Human superoxide dismutase 3, extracellular (SOD3) (NM_003102) ORF clone, Untagged (Cat#: NEP-0521-R0808)
- Human apolipoprotein E (APOE) (NM_000041) ORF clone, Untagged (Cat#: NEP-0421-R0232)
- Human superoxide dismutase 1, soluble (SOD1) (NM_000454) ORF clone, TurboGFP Tagged (Cat#: NEP-0521-R0748)
- NeuroBiologics™ Human Cerebrospinal Fluid (Cat#: NRZP-0822-ZP491)
- NeuroBiologics™ Pig Cerebrospinal Fluid (Cat#: NRZP-0822-ZP498)
- NeuroBiologics™ Mouse Cerebrospinal Fluid (Cat#: NRZP-0822-ZP497)
- NeuroBiologics™ Monkey Cerebrospinal Fluid (Cat#: NRZP-0822-ZP495)
- NeuroBiologics™ Rat Cerebrospinal Fluid (Cat#: NRZP-0822-ZP496)
- NeuroPro™ Anti-EPO BBB Shuttle Protein (Cat#: NRZP-0423-ZP508)
- NeuroPro™ Anti-SGSH BBB Shuttle Protein (Cat#: NRZP-0423-ZP505)
- NeuroPro™ Anti-IDS BBB Shuttle Protein (Cat#: NRZP-0423-ZP503)
- NeuroPro™ Anti-TNFR BBB Shuttle Protein (Cat#: NRZP-0423-ZP510)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP500)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP509)
- NeuroPro™ Anti-TNFR BBB Shuttle Protein (Cat#: NRZP-0423-ZP501)
- NeuroPro™ Anti-IDUA BBB Shuttle Protein (Cat#: NRZP-0423-ZP498)
- NeuroPro™ Anti-Erythropoietin BBB Shuttle Protein (Cat#: NRZP-0423-ZP499)
- NeuroPro™ Anti-NAGLU BBB Shuttle Protein (Cat#: NRZP-0423-ZP506)