Post by Admin on Aug 4, 2022 19:35:34 GMT
The importance of non-canonical autophagy pathways in Alzheimer’s disease pathology and potential therapies
researchfeatures.com/importance-non-canonical-autophagy-pathways-alzheimers-disease-pathology-potential-therapies/
Autophagy is a vital process in the body: cells degrade unwanted or dysfunctional components to recycle nutrients, maintain energetic substrates, and support cellular homeostasis. However, defects in autophagy can lead to neuroinflammation and progressive neurodegenerative diseases such as Alzheimer’s disease. Conventional autophagy pathways have been well established by past research. Now, Dr Bradlee L Heckmann, USF Health Neuroscience Institute, along with Dr Douglas R Green, discovered a non-conventional autophagic mechanism: the microtubule-associated protein light-chain 3 (LC3)-associated endocytosis (LANDO). LANDO plays a major role in regulating cellular energetics, cell death, and neuronal function.
The key phenomena involved in the inception and progression of neurodegenerative diseases such as Alzheimer’s disease (AD) are neuroinflammation and neurodegeneration. Conventional pathways of macro-autophagy (hereby referred to as autophagy) involve the removal of damaged organelles, protein aggregates, and other cellular components through internalisation and endocytosis (a process by which a cell engulfs a foreign protein and lyses it internally) to maintain cellular and metabolic homeostasis. Proteins like Beclin1, ATG5, and ATG7 are instrumental in regulating such autophagic pathways. They also function in the brain’s innate immune microglial cells to induce receptor-mediated endocytosis and prevent excess build-up of ß-amyloid (Aβ)-peptide oligomers, a classic hallmark for AD progression. Additionally, autophagy also regulates various immune pathways: it controls the secretion of pro-inflammatory cytokines such as type-I interferon (INF) and interleukin (IL)-1ß by targeting the IL-1ß precursor and pro-IL-1ß for degradation.
Microglial cells, the flag-bearers of immunity in the central nervous system (CNS), undergo autophagic mechanisms with the help of toll-like receptors (TLRs), Fc receptors, Immunoglobulin (Ig)-superfamily receptors, scavenger receptors (SRs), and complement receptors. The expressions of Beclin1, ATG5, and ATG7 reduce proportionally with age. Unsurprisingly, patients with neurodegenerative disorders like AD have shown drastically reduced levels of these proteins.
researchfeatures.com/importance-non-canonical-autophagy-pathways-alzheimers-disease-pathology-potential-therapies/
Autophagy is a vital process in the body: cells degrade unwanted or dysfunctional components to recycle nutrients, maintain energetic substrates, and support cellular homeostasis. However, defects in autophagy can lead to neuroinflammation and progressive neurodegenerative diseases such as Alzheimer’s disease. Conventional autophagy pathways have been well established by past research. Now, Dr Bradlee L Heckmann, USF Health Neuroscience Institute, along with Dr Douglas R Green, discovered a non-conventional autophagic mechanism: the microtubule-associated protein light-chain 3 (LC3)-associated endocytosis (LANDO). LANDO plays a major role in regulating cellular energetics, cell death, and neuronal function.
The key phenomena involved in the inception and progression of neurodegenerative diseases such as Alzheimer’s disease (AD) are neuroinflammation and neurodegeneration. Conventional pathways of macro-autophagy (hereby referred to as autophagy) involve the removal of damaged organelles, protein aggregates, and other cellular components through internalisation and endocytosis (a process by which a cell engulfs a foreign protein and lyses it internally) to maintain cellular and metabolic homeostasis. Proteins like Beclin1, ATG5, and ATG7 are instrumental in regulating such autophagic pathways. They also function in the brain’s innate immune microglial cells to induce receptor-mediated endocytosis and prevent excess build-up of ß-amyloid (Aβ)-peptide oligomers, a classic hallmark for AD progression. Additionally, autophagy also regulates various immune pathways: it controls the secretion of pro-inflammatory cytokines such as type-I interferon (INF) and interleukin (IL)-1ß by targeting the IL-1ß precursor and pro-IL-1ß for degradation.
Microglial cells, the flag-bearers of immunity in the central nervous system (CNS), undergo autophagic mechanisms with the help of toll-like receptors (TLRs), Fc receptors, Immunoglobulin (Ig)-superfamily receptors, scavenger receptors (SRs), and complement receptors. The expressions of Beclin1, ATG5, and ATG7 reduce proportionally with age. Unsurprisingly, patients with neurodegenerative disorders like AD have shown drastically reduced levels of these proteins.