Table 3.

Summary of preclinical studies of MANF in rodent Parkinson’s disease models.

Disease model	Delivery method of MANF	Time of MANF delivery	Outcomes of MANF therapy	References
6-OHDA to the striatum	Single protein injection to the striatum	Prior to lesion	Reduced rotations, improved survival of TH+ neurons in the SN	(13)
		Post lesion	Reduced rotations, no significant improvement in the survival of TH+ cells in the SN
	Single protein injection to the striatum	Post lesion	Reduced rotations, improved survival of TH+ neurons in the caudal part of SN	(119)
	Chronic protein delivery to the striatum	Post lesion	No significant improvement in rotations, TH+ cell survival or TH+ fiber density	(14)
	Gene delivery via AAV9 vector to the striatum	Post lesion	Promoted survival of TH+ neurons in the SN, improved TH+ fiber density, increased dopamine levels, reduced rotations	(120)
	Gene delivery via lentivirus vector to the striatum	Time of the lesion	No significant improvement in the survival of TH+ cells in the SN or striatal TH+ fibers, or in rotations	(109)
	Gene delivery via lentivirus vector to the SN	Time of the lesion	Improved survival of TH+ cells in the SN, no improvement in rotational behavior
	Gene delivery via AAV8 vector to the SN	Prior to lesion	Improved motor behavior, improved survival of TH+ neurons in the SN, reduced activation of microglia	(121)
MPTP	Single protein injection to the striatum bilaterally	Time of the lesion	Improved motor behavior, increase in striatal dopamine and its metabolites, protection of TH+ cells in the SN	(122)
Rotenone	Gene delivery via AAV8 vector to the SN	Prior to lesion	Improved motor behavior, improved survival of TH+ cells in the SN	(123)

AAV, adeno-associated virus; SN, substantia nigra; TH, tyrosine hydroxylase.