Table 3.

Summary of current therapeutic approaches investigated experimentally or in clinical trials. https://www.clinicaltrials.gov, accessed on 3 August 2023.

Compound	Target	Effect	Clinical Trial	Clinical Trial PD	Ref.
Lovastatin	HMG-CoA reductase	reduces α-syn accumulation and its phosphorylation in vitro in HEK293 cells, SH-SY5Y cells, and in primary human neurons and in vivo in different transgenic mouse models that neuronally overexpress human α-syn	rheumatoid arthritis, cancer, etc.	Phase II	[212,213,214]
Simvastatin	HMG-CoA reductase	prevents MPTP-induced striatal dopamine depletion and protein tyrosine nitration in mice, and protects dopaminergic neurons in the substantia nigra, attenuates the expression of proinflammatory molecules, and improves motor deficits in the MPTP model of PD	hyper-lipidemia, diabetes, MS, etc.	Phase II	[212,215,216]
Myriocin	de novo ceramide synthesis	reduced oxidative stress and inflammation and increased vesicular trafficking in SH-SY5Y cells treated with α-syn fibrils	no	no	[217]
Ellagic acid	α-syn	polyphenolic compound that has an inhibitory effect toward oligomerization and fibrillation of α-syn in vitro, reduces α-syn aggregation, and increases cell survival	prostate cancer phase III	no	[218]
Squalamine	competitive of α-syn	specifically inhibits the initiation of aggregation of α-syn and alleviates its toxicity in neuronal cells and in a Caenorhabditis elegans model of PD	macular degeneration phase II and III	no	[219]
Nilotinib	α-syn kinase c-Abl	enhanced clearance of α-syn, reduced neurotoxicity, and improved motor behavior in a mouse model of PD	AD phase 3, leukemia, etc.	no	[220]
MC1568	class IIa histone deacetylases	increased neurite density and cell survival and protected against the neurotoxin-treated SY5Y cells	cancer	no	[221]
VX-765	caspase-1	reduces neurodegeneration, motor symptoms, and neuroinflammation in a mouse model of MSA	no	no	[222]
Arachidonic acid	α-syn	essential FA that induces the formation of ordered, α-helical structured α-syn multimers being resistant to fibrillation	autism, fibrosis, diabetes, etc.	no	[223]
Niacin/Nicotin-amide	Poly (ADP-ribose) polymerase	precursor of NADH and cofactor of mitochondrial enzymes that protects from MPTP-induced neurotoxicity in mice and prevents mitochondrial dysfunction in a cellular model and improves motor behavior in a Drosophila model of PD	hyperlipidemia, myopathy, etc.	interventional study	[224,225,226]
Deferiprone	ferric ions	iron chelator that reduces iron depositions in the substantia nigra accompanied by alleviated motor deficits in a clinical trial in early PD	HIV, ALS, heart disease, etc.	failed	[227]