TY - JOUR

T1 - Neuroregeneration in Parkinson's Disease

T2 - From Proteins to Small Molecules

AU - Sidorova, Yulia A.

AU - Volcho, Konstantin P.

AU - Salakhutdinov, Nariman F.

N1 - Publisher Copyright: © 2019 Bentham Science Publishers.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, the lifetime risk of developing this disease is 1.5%. Motor diagnostic symptoms of PD are caused by degeneration of nigrostriatal dopamine neurons. There is no cure for PD and current therapy is limited to supportive care that partially alleviates disease signs and symptoms. As diagnostic symptoms of PD result from progressive degeneration of dopamine neurons, drugs restoring these neurons may significantly improve treatment of PD. METHOD: A literature search was performed using the PubMed, Web of Science and Scopus databases to discuss the progress achieved in the development of neuroregenerative agents for PD. Papers published before early 2018 were taken into account. RESULTS: Here, we review several groups of potential agents capable of protecting and restoring dopamine neurons in cultures or animal models of PD including neurotrophic factors and small molecular weight compounds. CONCLUSION: Despite the promising results of in vitro and in vivo experiments, none of the found agents have yet shown conclusive neurorestorative properties in PD patients. Meanwhile, a few promising biologicals and small molecules have been identified. Their further clinical development can eventually give rise to disease-modifying drugs for PD. Thus, intensive research in the field is justified.

AB - BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, the lifetime risk of developing this disease is 1.5%. Motor diagnostic symptoms of PD are caused by degeneration of nigrostriatal dopamine neurons. There is no cure for PD and current therapy is limited to supportive care that partially alleviates disease signs and symptoms. As diagnostic symptoms of PD result from progressive degeneration of dopamine neurons, drugs restoring these neurons may significantly improve treatment of PD. METHOD: A literature search was performed using the PubMed, Web of Science and Scopus databases to discuss the progress achieved in the development of neuroregenerative agents for PD. Papers published before early 2018 were taken into account. RESULTS: Here, we review several groups of potential agents capable of protecting and restoring dopamine neurons in cultures or animal models of PD including neurotrophic factors and small molecular weight compounds. CONCLUSION: Despite the promising results of in vitro and in vivo experiments, none of the found agents have yet shown conclusive neurorestorative properties in PD patients. Meanwhile, a few promising biologicals and small molecules have been identified. Their further clinical development can eventually give rise to disease-modifying drugs for PD. Thus, intensive research in the field is justified.

KW - BDNF

KW - BDNF mimetics

KW - dopamine neurons

KW - GDNF

KW - GDNF mimetics

KW - neuroprotection

KW - Neurorestoration

KW - neurotrophic factors.

KW - Parkinson's disease

KW - RET agonists

KW - Trk agonists

KW - MITOCHONDRIAL BIOGENESIS

KW - ADRENAL-MEDULLARY AUTOGRAFTS

KW - SUBSTANTIA-NIGRA

KW - MIDBRAIN DOPAMINERGIC-NEURONS

KW - RAT MODEL

KW - NERVE GROWTH-FACTOR

KW - NEUROTROPHIC FACTOR GDNF

KW - neurotrophic factors

KW - MOUSE MODEL

KW - DOUBLE-BLIND

KW - NEURAL PRECURSOR CELLS

KW - Dopamine neurons

KW - Neurotrophic factors

KW - Neurorestoration, neuroprotection

KW - Parkinson’s disease

UR - http://www.scopus.com/inward/record.url?scp=85062087375&partnerID=8YFLogxK

U2 - 10.2174/1570159X16666180905094123

DO - 10.2174/1570159X16666180905094123

M3 - Review article

C2 - 30182859

AN - SCOPUS:85062087375

VL - 17

SP - 268

EP - 287

JO - Current Neuropharmacology

JF - Current Neuropharmacology

SN - 1570-159X

IS - 3

ER -