Marine-Derived Components: Can They Be a Potential Therapeutic Approach to Parkinson's Disease?

Abstract

The increase in the life expectancy average has led to a growing elderly population, thus leading to a prevalence of neurodegenerative disorders, such as Parkinson's disease (PD). PD is the second most common neurodegenerative disorder and is characterized by a progressive degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). The marine environment has proven to be a source of unique and diverse chemical structures with great therapeutic potential to be used in the treatment of several pathologies, including neurodegenerative impairments. This review is focused on compounds isolated from marine organisms with neuroprotective activities on in vitro and in vivo models based on their chemical structures, taxonomy, neuroprotective effects, and their possible mechanism of action in PD. About 60 compounds isolated from marine bacteria, fungi, mollusk, sea cucumber, seaweed, soft coral, sponge, and starfish with neuroprotective potential on PD therapy are reported. Peptides, alkaloids, quinones, terpenes, polysaccharides, polyphenols, lipids, pigments, and mycotoxins were isolated from those marine organisms. They can act in several PD hallmarks, reducing oxidative stress, preventing mitochondrial dysfunction, α-synuclein aggregation, and blocking inflammatory pathways through the inhibition translocation of NF-kB factor, reduction of human tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6). This review gathers the marine natural products that have shown pharmacological activities acting on targets belonging to different intracellular signaling pathways related to PD development, which should be considered for future pre-clinical studies.

Keywords: ageing society; marine bioactive compounds; neurodegenerative disease; neuroinflammation; neurological disorders; neuroprotective activity; seaweeds.

Figure 1

Percentage of global population with age above 65 years old. Adapted from the “World Statistic” data platform, 2021.

Figure 2

Physiological processes related to Parkinson’s disease pathogenesis. Created with BioRender.com (accessed on 6 July 2023).

Figure 3

New marine natural products (%) isolated from marine organisms between 1977 and 2021 (Adapted from Faulkner, 1984–2002; Blunt et al., 2003–2018; Carroll et al., 2019; Carroll et al., 2020; Carroll et al., 2021; Carroll et al., 2022; Carroll et al., 2023) [48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66].

Figure 4

Chemical structures of marine natural products isolated from bacteria: NP7 (1), mannosylglycerate (2), piloquinone A (3), piloquinone B (4).

Figure 5

Chemical structures of marine natural products isolated from fungi: neoechinulin A (5), xyloketal B (6), secalonic acid A (7), 6-hydroxy-N-acetyl-b-oxotryptamine (8), 3-methylorsellinic acid (9), 8-methoxy-3,5-dimethylisochroman-6-ol (10), candidusin A (11), 4``-dehydroxycandidusin A (12), diketopiperazine mactanamide (13), and asperpendoline (14).

Figure 6

Chemical structures of marine natural products isolated from mollusks: Eicosapentaenoic acid (15), docosahexaenoic acid (16), and astaxanthin (17).

Figure 7

Chemical structures of marine natural products isolated from sea snails: α-Conotoxin (18).

Figure 8

Chemical structures of marine natural products isolated from sea cucumber: SCG-1 (19), SCG-2 (20), SCG-3 (21), decanoic acid (22), and palmitic acid (23).

Figure 9

Chemical structures of marine natural products isolated from seaweeds: fucoxanthin (24), dieckol (25), polymannosic acid (26), polyguluronic acid (27), eleganolone (28), and loliolide (29).

Figure 10

Chemical structures of marine natural products isolated from soft corals: austrasulfone (30), 1-tosylpentan-3-one (31), 11-dehydrosinulariolide (32), and sarcophytolide (33).

Figure 11

Chemical structures of marine natural products isolated from sponges: gracilins (A, H, K, J and L) (34–38), tetrahydroaplysulphurin-1 (39), sarain A (40), hymenin (41), hymenialdisine (42), psammaplysene A (43), 24-hydroperoxy-24-vinylcholesterol (44), 29-hydroperoxystigmasta-5,24(28)-dien-3-ol (45), iotrochotazine (46), jaspamycin (47), aerothionin (48), and aerophobin-2 (49).

Figure 12

Chemical structures of marine-derived products used in clinical trials against Parkinson’s disease: docosahexaenoic acid (50), inosine (51), pramipexole (52), CEP-1347 (53), and ganglioside GM1 (54).