The causes of neurodegenerative disorders are multiple, and for most of them a mechanistic understanding
is still lacking. However, neurodegenerative diseases such as Alzheimer disease (AD), amyotrophic lateral sclerosis
(ALS) and Parkinson disease (PD) all share common features that include elevated oxidative stress levels and
impaired energy metabolism in the nervous system. Most of the current treatments are only successful at alleviating
some of the pathological symptoms, but fail at preventing neurodegeneration. There is therefore an urgent need for
innovative and more efficient treatments for neurodegenerative disorders.
We review here the central role played by astrocytes in the regulation of brain homeostasis, protection and function by supporting neuronal
health and activity. In particular, astrocytes are key partners of neuronal metabolism, notably through activation of the astrocyteneuron
lactate shuttle (ANLS). They also control the levels of extracellular glutamate, production of antioxidant molecules, disposal of
neuronal waste products, storage of energy in the form of glycogen, and expression of neurotrophic factors. These mechanisms, which
are key for brain activity and cognition, also largely contribute to neuronal degeneration in pathological situations.
Thus, as astrocytes appear to play a key role in the etiology of neurodegenerative disorders, a growing interest has arisen for astrocytemediated
pathways as targets for drugs that aim at treating the root causes of the pathology. We present here the most recent and promising
astrocyte-based therapeutic approaches - from fundamental discoveries to clinical trials - that intent to sustain neuronal health and
function in neurodegenerative disorders.