Abstract
Among nutraceuticals, phytochemical-rich compounds represent a source of naturally-derived bioactive principles, which are extensively studied for potential beneficial effects in a variety of disorders ranging from cardiovascular and metabolic diseases to cancer and neurodegeneration. In the brain, phytochemicals produce a number of biological effects such as modulation of neurotransmitter activity, growth factor induction, antioxidant and anti-inflammatory activity, stem cell modulation/neurogenesis, regulation of mitochondrial homeostasis, and counteracting protein aggregation through modulation of protein-folding chaperones and the cell clearing systems autophagy and proteasome. In particular, the ability of phytochemicals in restoring proteostasis through autophagy induction took center stage in recent research on neurodegenerative disorders such as Parkinson’s disease (PD). Indeed, autophagy dysfunctions and α-syn aggregation represent two interdependent downstream biochemical events, which concur in the parkinsonian brain, and which are targeted by phytochemicals administration. Therefore, in the present review we discuss evidence about the autophagy-based neuroprotective effects of specific phytochemical-rich plants in experimental parkinsonism, with a special focus on their ability to counteract alpha-synuclein aggregation and toxicity. Although further studies are needed to confirm the autophagy-based effects of some phytochemicals in parkinsonism, the evidence discussed here suggests that rescuing autophagy through natural compounds may play a role in preserving dopamine (DA) neuron integrity by counteracting the aggregation, toxicity, and prion-like spreading of α-syn, which remains a hallmark of PD.
Highlights
Nutraceuticals include a broad range of naturally occurring, though different compounds such as functional foods, fortified foods, and dietary supplements which as a common signature promote human and animal health and wellness [1,2]
This is due to the fact that autophagy regulates the turnover of key proteins and organelles which are involved in these cell processes, and again, a mutual interplay exists between autophagy machinery and secretory/trafficking pathways, heat shock protein chaperones, apoptosis, growth factors, and inflammatory cascades
An impairment of the autophagy pathway is tightly intermingled with α-syn misfolding/aggregation/accumulation/spreading and, with the neurobiology of Parkinson’s disease (PD) and related “synucleinopathies” such as Dementia with Lewy Bodies (DLB), multisystem atrophy (MSA), pure autonomic failure (PAF), lysosomal storage diseases (LSD), and Meth abuse [127,131,187,188,189,190,191]
Summary
Nutraceuticals include a broad range of naturally occurring, though different compounds such as functional foods, fortified foods, and dietary supplements which as a common signature promote human and animal health and wellness [1,2]. Phytochemicals from the plants represented here confer neuroprotection by preventing or reverting (blue arrows) this pathological cascade, starting from autophagy induction to inhibition of α-syn aggregation, neuroinflammation, and oxidative stress
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