The present review examines whether the microRNA 7 (miR-7) holds potential for slowing
Parkinson's disease (PD) progression. First, the accurate expression of miR-7 allows for normal development,
physiology, and neurogenesis in the central nervous system, also keeping alpha-synuclein
(α-Syn) at the physiological level. Second, patients with PD and parkinsonian MPTP-induced animals
exhibit a significant decrease of miR-7 in brain areas associated with dopaminergic neurodegeneration.
Depletion of miR-7 in the substantia nigra of clinical samples is related to α-Syn accumulation,
loss of dopaminergic cells, and reduction of dopamine in the striatum. Therefore, the goal of a miR-7-
replacement therapy is to downregulate α-Syn and other PD-related genes, achieving multi-target
benefits regarding oxidative stress, mitochondrial health, cell glycolysis, apoptosis, and inhibition of
inflammasome activation. While a disease-modifying drug is a major unmet need for the clinical management
of PD, an miR-7-replacement therapy presents a striking potential against critical mechanisms
of neuropathology. Such innovative treatment would reduce α-Syn accumulation in the Lewy
bodies and preserve remaining neurons yet viable at the time of diagnosis, thus slowing disease progression
from the early phase of PD characterized by a relatively mild motor impairment to an advanced
and more disabling stage.
Keywords: miR-7, Parkinson's disease, Neurodegeneration, RNAi, MicroRNA, Synuclein, Lewy body, Synucleinopathy.
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