Abstract:
:Historically considered as accessory cells to neurons, there is an increasing interest in the role of astrocytes in normal and pathological conditions. Astrocytes are involved in neurotransmitter recycling, antioxidant supply, ion buffering and neuroinflammation, i.e. a lot of the same pathways that go astray in Alzheimer's disease (AD). AD remains the leading cause of dementia in the elderly, one for which there is still no cure. Efforts in AD drug development have largely focused on treating neuronal pathologies that appear relatively late in the disease. The neuroenergetic hypothesis, however, focuses on the early event of glucose hypometabolism in AD, where astrocytes play a key role, caused by an imbalanced neuron-astrocyte lactate shuttle. This further results in a state of oxidative stress and neuroinflammation, thereby compromising the integrity of astrocyte-neuron interaction. Compromised astrocytic energetics also enhance amyloid generation, further increasing the severity of the disease. Additionally, apolipoprotein E (APOE), the major genetic risk factor for AD, is predominantly secreted by astrocytes and plays a critical role in amyloid clearance and regulates glucose metabolism in an amyloid-independent manner. Thus, boosting the neuroprotective properties of astrocytes has potential applications in delaying the onset and progression of AD. This review explores how the metabolic dysfunction arising from astrocytes acts as a trigger for the development of AD.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Zulfiqar S,Garg P,Nieweg Kdoi
10.1515/hsz-2019-0140subject
Has Abstractpub_date
2019-08-27 00:00:00pages
1113-1127issue
9eissn
1431-6730issn
1437-4315pii
/j/bchm.just-accepted/hsz-2019-0140/hsz-2019-0140.journal_volume
400pub_type
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