Marine-Natural Compounds

Parkinson’s disease (PD) is a common neurodegenerative disease that mainly occurs in the elderly. The main pathological changes of PD included the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc); the decrease of dopamine content in the striatum, and the formation of α-synuclein aggregates in the brain. The death of DA neurons in SNc could further inhibit thalamic activity, and reduce the excitatory input to the motor cortex; resulting in slow movements and limbs stiff in PD patients.

Although the etiology of PD is still unclear, the death of DA neurons during PD progress to with the abnormal aggregation of α-synuclein, the elevation of oxidative stress; the decrease of mitochondrial functions, and the increase of neuroinflammation. Anti-PD drugs mainly aim to relieve motor and non-motor symptoms, and produce neuroprotective effects. Clinically used anti-PD drugs include dopamine precursors (levodopa and carbidopa); dopamine agonists (pramipexole, ropinirole, rotigotine and apomorphine), catechol-O-methyl transferase (COMT) inhibitors and monoamine oxidase B (MAO-B) inhibitors (selegiline, rasagiline and safinamid).

PD is a complex disease with many pathological factors. Therefore, it is possible to discover drugs that work synergistically with multiple targets of PD. Most clinically used anti-PD drugs are producing by acting on a single target with a certain degree of side effects. Marine-derived compounds usually contain reactive groups such as -OH, -NH2, and –SH in their chemical structures; might act as anti-oxidants.

The marine-derived compounds

Other functional groups of marine-derived compounds might enable them to act on anti-PD targets such as α-synuclein, MAO-B and other key proteins in the signaling pathways. Therefore, marine-derived compounds, in this review, might developed as anti-PD leads with multiple targets. Many clinical trials on PD aim to improve the efficacy of drugs already used in the treatment of PD.

This is partially because of the difficulty of finding novel natural compounds from terrestrial organisms. The sea is a treasure for discovering novel natural compounds. Marine-derived compounds have continuously entered into clinical trials against different diseases, and have become one of the important sources of drug development. Recently, the anti-AD marine-a GV-971 has successfully passed phase III clinical trial in China, and has gradually advanced in the process of drug application, indicating that marine-derived compounds could used to treat neurodegenerative disorders.

Some marine-derived compounds, in this review, have entered clinical trials with the aim of treating PD;  further providing a support that novel anti-PD drugs might developed from marine-derived compounds. With the increasing exploration of the ocean, more marine drugs have emerged. However, they have only touched the tip of the iceberg for marine resources. Marine organisms could produce a large number of chemicals with novel structures and diverse activities.

Isolated from marine organisms

In addition to compounds that are directly extracted or isolated from marine organisms, designed compounds could modified and synthesized from the marine-derived leads. In this review, 34 marine-derived compounds with pharmacological potential on PD therapy have been summarized; among which 5 compounds have entered into anti-PD clinical trials.

Through high-throughput screening and combinatorial chemistry applications; more drug candidates will found from the marine natural product library for the treatments of PD; especially those could be synthesized directly, or could obtained in large quantities by fermentation or culture. They anticipated that further focusing on natural products from marine sources may a promising idea for developing anti-PD leads.