MINIREVIEW
Emerging pathways in genetic Parkinson’s disease:
Autosomal-recessive genes in Parkinson’s disease –
a common pathway?
Julia C. Fitzgerald and Helene Plun-Favreau
Department of Molecular Neuroscience, Institute of Neurology, University College London, UK
Parkinson’s disease (PD) is a common neurode-
generative disorder with no known cure, estimated to
affect 4 million people worldwide. The disease is char-
acterized by the degeneration of dopaminergic neurons
in the substantia nigra pars compacta and the presence
of protein inclusions called Lewy bodies. The death of
dopamine neurons in the substantia nigra pars com-
pacta alters neurotransmitter balance in the striatum
resulting in the progressive loss of movement control,
the principal hallmark of PD, encompassing clinical
features such as resting tremor, bradykinesia, postural
instability and rigidity.
The most common form of PD is sporadic; there
are, however, inherited forms of PD, accounting for
5–10% of cases. Little is known about how or why
neurons die in PD, but similarities between both forms
of the disease have led researchers to believe that a
common set of molecular mechanisms may underlie
PD aetiology.
To date, six genes have been implicated in the
pathogenesis of PD, a-synuclein, Parkin, PTEN-
induced putative kinase 1 (PINK1), DJ-1, leucine-rich
repeat kinase 2 (LRRK2) and ATP13A2. Mutations in
the genes encoding a-synuclein, LRRK2 and ATP13A2
cause autosomal-dominant forms of parkinsonism.

Parkinson’s disease; PINK1, PTEN-induced putative kinase 1; PTEN, phosphatase and tensin homologue deleted on chromosome 10;
TRAP1, tumour necrosis factor receptor-associated protein 1; UCH-L1, ubiquitin C-terminal hydrolase L1; UPS, ubiquitin proteasomal system.
5758 FEBS Journal 275 (2008) 5758–5766 ª 2008 The Authors Journal compilation ª 2008 FEBS
Autosomal-recessive Parkinson’s
disease genes and proteins
Parkin (PARK2)
Mutations in PARK2 were first reported in patients
with autosomal-recessive juvenile-onset PD (AR-JP) [1]
and are now known to be the predominant cause of
early-onset parkinsonism. A large number of patho-
genic mutations have been identified in Parkin, present
in  50% of individuals with AR-JP, and 77% of
sporadic cases with disease onset before the age of 20
[2]. Clinically, PD patients with mutations in PARK2
suffer a slow progression of the disease commonly
associated with early-onset dystonia and are l-Dopa
responsive [3]. Pathological studies on AR-JP patients
with Parkin mutations have revealed a lack of Lewy
body inclusions [4] except in some later onset cases
[5,6].
Parkin localizes predominantly to the cytosol and
cellular vesicles [7–9]. However, part of the cellular
Parkin pool associates with the outer mitochondrial
membrane [8]. Parkin is an E3 ubiquitin ligase, an
essential component of the ubiquitin-proteasomal
system (UPS) [7]. Parkin also has a proteasome-inde-
pendent role and a number of putative substrates for
Parkin have been described, including proteins impli-
cated in PD such as synphilin-1 and a glycosylated
form of a-synuclein [10]. It is worth noting, however,

DJ-1 mutation is a large deletion unlikely to produce
any protein. The other, a point mutation (L166P), has
been studied extensively. Later, several studies led to
the identification of a number of other pathogenic
mutations causing familial PD [21]. Clinically, age of
onset is usually in the third decade with a slow disease
progression and a good response to l-Dopa. DJ-1 is
localized to both the nucleus and cytoplasm in differ-
ent cell types [22,23], although a pool of wild-type
DJ-1 has been shown to localize to the mitochondria
[24]. The L166P mutant protein has been shown to be
associated with loss of nuclear localization and trans-
location to mitochondria [25] although this was not
confirmed in other studies [24]. Conversely, localiza-
tion of wild-type DJ-1 at the mitochondria is suggested
to be a requirement for neuroprotection [26]. DJ-1 has
been ascribed various functions, notably in resistance
to oxidative stress [11], but also transcription, cell sig-
nalling, apoptosis [27,28] and aggregation of a-synuc-
lein [29]. The protein may also act as a chaperone.
Finally, studies suggested that DJ-1 could possess cys-
teine protease activity. However, the protease activity
of DJ-1 is still a matter of debate [30,31]. But perhaps
the most important function with regard to PD is its
putative role in oxidative stress. DJ-1 is thought to
protect neurons from oxidative stress [19,32,33]
although exactly how it exerts its protective effects
remains to be determined.
Molecular pathways of
neurodegeneration in PD

rotenone-induced cytotoxicity [40]. Furthermore, it has
been reported very recently that germline deletion of
the PINK1 gene in mice significantly impairs mito-
chondrial functions and provides critical protection
against oxidative stress [41,42]. Neurons with reduced
levels of endogenous DJ-1 were also sensitized to
toxicity elicited by rotenone [43] and Drosophila DJ-1
mutants were selectively sensitive to environmental
toxins associated with PD [44].
Parkin and PINK1 have been shown to be located,
at least in part, to the mitochondria. In Drosophila
models of PINK1, several studies [45–47] strongly
suggested that PINK1 acts upstream of Parkin in a
common pathway that influences mitochondrial integ-
rity in a subset of tissues (including flight muscle and
dopaminergic neurons). Recent studies suggest that
the PINK1⁄ Parkin pathway regulates mitochondrial
morphology in Drosophila and mammalian models
[48–50].
DJ-1 does not seem to operate in the same pathway as
Parkin and PINK1. Muscle and dopaminergic pheno-
types associated with Drosophila PINK1 inactivation
can be suppressed by the overexpression of Parkin, but
not DJ-1 [24]. Although there is less evidence for a direct
role of DJ-1 in mitochondrial function, the fact that
Drosophila lacking DJ-1 exhibit increased sensitivity to
environmental mitochondrial toxins [44,51] does point
to a role for DJ-1 in mitochondrial function.
Drosophila studies suggest that PINK1 is required
for mitochondrial function and that the PINK1 ⁄ Parkin

Proteasomal dysfunction and proteolytic stress
The proteasome is a large multi-catalytic proteinase
complex found in the nucleus and cytoplasm of
eukaryotic cells [56,57]. UPS dysfunction and proteo-
lytic stress are likely to contribute to dopaminergic
neurodegeneration [58]. Moreover, mutations in two
components of the UPS; Parkin and ubiquitin C-termi-
nal hydrolase-L1 (UCH-L1) [59] in familial PD
strongly supports the hypothesis that proteasomal
dysfunction may contribute to PD aetiology [57].
Notably knockdown of DJ-1 [60] and Parkin [61,62]
enhances susceptibility to proteasome inhibition in cell
models. In addition, DJ-1-deficient mice treated with
the mitochondrial complex I inhibitor paraquat display
decreased proteasome activities and increased levels of
ubiquitinated protein [63]. Finally, the UPS has also
been shown to be important for the regulation of
PINK1 stability [63] and the degradation of DJ-1
[30,64], PINK1 [65] and Parkin [66,67] mutant
proteins.
Chaperones may be key players in PD pathogenesis.
PINK1 has been shown to interact with the Hsp90
molecular chaperone and it was proposed that the
inhibition of this interaction might contribute to the
pathogenesis of PD [65]. Furthermore, PINK1 has
been suggested to protect against oxidative stress by
phosphorylating the mitochondrial chaperone tumour
necrosis factor receptor-associated protein 1 (TRAP1)
Autosomal recessive genes in Parkinson’s disease J. C. Fitzgerald and H. Plun-Favreau
5760 FEBS Journal 275 (2008) 5758–5766 ª 2008 The Authors Journal compilation ª 2008 FEBS

shift in the isoelectric point of DJ-1 [26,32,74] sug-
gesting self-oxidation. Embryonic stem cells deficient
in DJ-1 display increased sensitivity to oxidative
stress and proteasome inhibition [75]. Following
exposure to oxidative stress, DJ-1 associates with
Parkin, potentially linking these proteins into a com-
mon molecular pathway leading to nigral degenera-
tion and PD [76]. Parkin knockout mice have
revealed an essential role for Parkin in oxidative
stress [77] and Drosophila Parkin mutants show
increased sensitivity to oxidative stress [78]. Implica-
tion of PINK1 in oxidative stress processes has also
been strongly suggested: inactivation of Drosophila
PINK1 using RNAi suggested that PINK1 maintains
neuronal survival by protecting neurons against oxi-
dative stress [79]. In mammalian cell culture, PINK1
protects against oxidative stress-induced cell death by
suppressing cytochrome c release from mitochondria,
with the protective action of PINK1 depending on
its ability to phosphorylate the mitochondrial chaper-
one TRAP1 [68].
Protein phosphorylation and signalling pathways
PINK1 has a strongly predicted, conserved serine ⁄ thre-
onine kinase domain [12] and has been shown to
exhibit autophosphorylation activity [15,80,81] in vitro.
In vivo, PINK1 has been shown to phosphorylate the
mitochondrial chaperone TRAP1, protecting against
oxidative stress-induced apoptosis [68] and to be
important for the phosphorylation of HtrA2 upon
activation of the p38 pathway, preventing against

ability of dopaminergic cells to cope with toxic insults in
PD [87]. To date, no direct phosphorylation of DJ-1 or
PINK1 has been reported.
Conclusion
A common pathway to parkinsonism?
There has been a great deal of interest from the PD
scientific community in linking the familial-associated
genes in a common pathogenic pathway of neurode-
generation. To date, however, a single pathway unify-
ing these proteins has not been fully mapped out.
J. C. Fitzgerald and H. Plun-Favreau Autosomal recessive genes in Parkinson’s disease
FEBS Journal 275 (2008) 5758–5766 ª 2008 The Authors Journal compilation ª 2008 FEBS 5761
PINK1 and Parkin seem to function, at least in part,
in the same pathway, with PINK1 acting upstream of
Parkin. Moreover, a recent study has proposed a role
for Cdc37 ⁄ Hsp90 chaperones and Parkin on PINK1
subcellular distribution, providing further evidence for a
Parkin ⁄ PINK1 common pathogenic pathway in reces-
sive PD [16]. The role of the PINK1–Parkin pathway in
regulating mitochondrial function underscores the
importance of mitochondrial impairment as a key
molecular mechanism underlying PD. Overexpression
experiments in SH-SY5Y human neuroblastoma cells
have shown that DJ-1 specifically interacts with Parkin
under stress conditions. Specifically, this association is
mediated by pathogenic DJ-1 mutations and oxidative
stress [76]. These data suggest a link DJ-1 and Parkin in
a common pathway in mammals. A described case of
autosomal-recessive PD with digenic inheritance,
suggested that DJ-1 and PINK1 might physically inter-

mon point? Answering these questions requires a good
PD model. Drosophila and more recently zebrafish [92]
models have recapitulated many of the phenotypic and
pathologic features of PD, however, these models are
far-removed from human DA neurons. Both primary
neurons and human neuronal cell lines better represent
the cell types involved in PD, but have major limita-
tions [93]. Advances in the field of stem cell research
might open up a new route to develop a cell model
that more closely mirrors the disease situation in
humans. The use of induced pluripotent stem cells as a
research tool has become very promising following a
number of publications showing re-programming of
human fibroblasts carrying mutations to induced
pluripotent stem cells [94,95] and recently their differ-
entiation into specific neuronal subtypes [96].
Understanding the exact function of Parkin, PINK1,
DJ-1 and HtrA2 proteins in age-matched healthy
volunteer (and ideally relatives) neurons compared with
the neurons of patients with AR-JP may allow us to
Fig. 1. Protein products of AR-JP genes: Proposed cross-talk of
pathways. Extracellular and intracellular cues activate universal cell-
signalling cascades including MAPK and phosphatidylinositol
3-kinase (PI3K) pathways that can target HtrA2, PINK1, Parkin and
DJ-1. Likely these PD-associated proteins are part of a complex
network including various signalling pathways. Although DJ-1
appears to act slightly more independently than PINK1, Parkin and
HtrA2, these PD-associated proteins seem to act in extremely com-
plex, multistepped and related pathways. The complexity and
cross-talk may be important in fine-tuning of cellular responses,

N Engl J Med 342, 1560–1567.
3 Schapira AH (2008) Mitochondria in the aetiology and
pathogenesis of Parkinson’s disease. Lancet Neurol 7,
97–109.
4 Hayashi S, Wakabayashi K, Ishikawa A, Nagai H, Sai-
to M, Maruyama M, Takahashi T, Ozawa T, Tsuji S &
Takahashi H (2000) An autopsy case of autosomal-
recessive juvenile parsinsonism with a homozygous
exon 4 deletion in the parkin gene. Mov Disord 15, 884–
888.
5 Farrer M, Chan P, Chen R, Tan L, Lincoln S, Hernan-
dez D, Forno L, Gwinn-Hardy K, Petrucelli L, Hussey
J et al. (2001) Lewy bodies and parkinsonism in families
with parkin mutations. Ann Neurol 50, 293–300.
6 Pramstaller PP, Schlossmacher MG, Jacques TS, Scara-
velli F, Eskelson C, Pepivani I, Hedrich K, Adel S,
Gonzales-McNeal M, Hilker R et al. (2005) Lewy body
Parkinson’s disease in a large pedigree with 77 parkin
mutation carriers. Ann Neurol 58, 411–422.
7 Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa
S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka
K et al. (2000) Familial Parkinson disease gene product,
Parkin, is a ubiquitin-protein ligase. Nat Genet 3, 302–
305.
8 Darios F, Corti O, Lu
¨
cking CB, Hampe C, Muriel MP,
Abbas N, Gu WJ, Hirsch EC, Rooney T, Ruberg M
et al. (2003) Parkin prevents mitochondrial swelling and
cytochrome c release in mitochondria-dependent cell

602–616.
17 Haque EM, Thomas KJ, D’Souza C, Callaghan S, Kit-
ada T, Slack RS, Fraser P, Cookson MR, Tandon A &
Park DS (2008) Cytoplasmic Pink1 activity protects
neurons from dopaminergic neurotoxin MPTP. Proc
Natl Acad Sci USA 105, 1716–1721.
18 Hague S, Rogaeva E, Hernandez D, Gulick C, Single-
ton A, Hanson M, Johnson J, Weiser R, Gallardo M,
Ravina B et al. (2003) Early-onset Parkinson’s disease
caused by a compound heterozygous DJ-1 mutation.
Ann Neurol 54, 271–274.
19 Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ &
Wood NW (2003) The role of pathogenic DJ-1 muta-
tions in Parkinson’s disease. Ann Neurol 54, 283–286.
20 Hedrich K, Djarmati A, Scha
¨
fer N, Hering R, Wellen-
brock C, Weiss PH, Hilker R, Vieregge P, Ozelius LJ,
Heutink P et al. (2004) DJ-1 (PARK7) mutations are
less frequent than Parkin (PARK2) mutations in early-
onset Parkinson disease. Neurology 62, 389–394.
21 Alves da Costa C (2007) DJ-1: a newcomer in Parkin-
son’s disease pathology. Curr Mol Med 7, 650–657.
22 Yoshida K, Sato Y, Yoshike M, Nozawa S, Ariga H &
Iwamoto T (2003) Immunocytochemical localisation of
DJ-1 in human male reproductive tissue. Mol Reprod
Dev 66, 391–397.
23 Le Naour F, Misek DE, Krause MC, Deneux L, Giord-
ano TJ, Scholl S & Hanash SM (2001) Proteomics-
based identification of RS ⁄ DJ-1 as a novel circulating

cell death. Proc Natl Acad Sci USA 102, 9691–9696.
29 Shendelman S, Jonason A, Martinat C, Leete T & Abe-
liovich A (2004) DJ-1 is a redox-dependent molecular
chaperone that inhibits alpha-synuclein aggregate for-
mation. PLoS Biol 2, e362.
30 Olzmann JA, Brown K, Wilkinson KD, Rees HD, Huai
Q, Ke H, Levey AI, Li L & Chin LS (2004) Familial
Parkinson’s disease-associated L166P mutation disrupts
DJ-1 protein folding and function. J Biol Chem 279,
8506–8515.
31 Lee SJ, Kim SJ, Kim IK, Ko J, Jeong CS, Kim GH,
Park C, Kang SO, Suh PG, Lee HS et al. (2003) Crystal
structures of human DJ-1 and Escherichia coli Hsp31,
which share an evolutionarily conserved domain. J Biol
Chem 278, 44552–44559.
32 Zhou W, Zhu M, Wilson MA, Petsko GA & Fink AL
(2006) The oxidation state of DJ-1 regulates its chaper-
one activity toward alpha-synuclein. J Mol Biol 356,
1036–1048.
33 Abeliovich A & Flint Beal M (2006) Parkinsonism
genes: culprits and clues. J Neurochem 99, 1062–1072.
34 Abou-Sleiman PM, Muqit MM & Wood NW (2006)
Expanding insights of mitochondrial dysfunction in Par-
kinson’s disease. Nat Rev Neurosci 7, 207–219.
35 De Girolamo LA, Billett EE & Hargreaves AJ (2000)
Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
on differentiating mouse N2a neuroblastoma cells.
J Neurochem 75, 133–140.
36 Caneda-Ferron B, De Girolamo LA, Costa T, Beck
KE, Layfield R & Billett EE (2008) Assessment of the

causes mitochondrial functional defects and increased
sensitivity to oxidative stress. Proc Natl Acad Sci USA
105, 11364–11369.
42 Plun-Favreau H & Hardy J (2008) Pink1 in mitochon-
drial function. Proc Natl Acad Sci USA 105, 11041–
11042.
43 Liu F, Nguyen JL, Hulleman JD, Li L & Rochet JC
(2008) Mechanisms of DJ-1 neuroprotection in a cellu-
lar model of Parkinson’s disease. J Neurochem 105,
2435–2453.
44 Meulener M, Whitworth AJ, Armstrong-Gold CE, Riz-
zu P, Heutink P, Wes PD, Pallanck LJ & Bonini NM
(2005) Drosophila DJ-1 mutants are selectively sensitive
to environmental toxins associated with Parkinson’s dis-
ease. Curr Biol 15, 1572–1577.
45 Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol
JH, Yoo SJ, Hay BA & Guo M (2006) Drosophila
pink1 is required for mitochondrial function and inter-
acts genetically with Parkin. Nature 441, 1162–1166.
46 Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E,
Kim J, Shong M, Kim JM et al. (2006) Mitochondrial
dysfunction in Drosophila PINK1 mutants is comple-
mented by Parkin. Nature 441, 1157–1161.
47 Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang
JW, Yang L, Beal MF, Vogel H & Lu B (2006) Mito-
chondrial pathology and muscle and dopaminergic neu-
ron degeneration caused by inactivation of Drosophila
Pink1 is rescued by Parkin. Proc Natl Acad Sci USA
103, 10793–10798.
48 Poole AC, Thomas RE, Andrews LA, McBride HM,

asomal stress. J Neurochem 98, 156–169.
54 Lin W & Kang UJ (2008) PINK1 characterization of
processing, stability, and subcellular localization. J Neu-
rochem 106, 464–474.
55 Plun-Favreau H, Klupsch K, Moisoi N, Gandhi S,
Kjaer S, Frith D, Harvey K, Deas E, Harvey RJ,
McDonald N et al. (2007) The mitochondrial protease
HtrA2 is regulated by Parkinson’s disease-associated
kinase PINK1. Nat Cell Biol 9, 1243–1252.
56 De Martino GN & Slaughter CA (1999) The protea-
some, a novel protease regulated by multiple mecha-
nisms. J Biol Chem 274, 22123–22126.
57 Tanaka K & Chiba T (1998) The proteasome: a pro-
tein-destroying machine. Genes Cells 3, 499–510.
58 Dawson TM & Dawson VL (2003) Molecular pathways
of neurodegeneration in Parkinson’s disease. Science
302, 819–822.
59 Leroy E, Boyer R, Auburger G, Leube B, Ulm G,
Mezey E, Harta G, Brownstein MJ, Jonnalagada S,
Chernova T et al. (1998) The ubiquitin pathway in
Parkinson’s disease. Nature 395, 451–452.
60 Yokota T, Sugawara K, Ito K, Takahashi R, Ariga H
& Mizusawa H (2003) Down regulation of DJ-1
enhances cell death by oxidative stress, ER stress, and
proteasome inhibition. Biochem Biophys Res Commun
312, 1342–1348.
61 Petrucelli L, O’Farrell C, Lockhart PJ, Baptista M,
Kehoe K, Vink L, Choi P, Wolozin B, Farrer M,
Hardy J et al. (2002) Parkin protects against the toxicity
associated with mutant a-synuclein: proteasome dys-

defenses, and the proteasome. J Biol Chem 277, 28572–
28577.
68 Pridgeon JW, Olzmann JA, Chin LS & Li L (2008)
PINK1 protects against oxidative stress by phosphory-
lating mitochondrial chaperone TRAP1. PLoS Biol 5,
1494–1503.
69 Young JC & Hartl FU (2003) A stress sensor for the
bacterial periplasm. Cell 113, 1–2.
70 Moore DJ, West AB, Dikeman DA, Dawson VL &
Dawson TM (2008) Parkin mediates the degradation-
independent ubiquitination of Hsp70. J Neurochem 105,
1806–1819.
71 Kahle PJ & Haass C (2004) How does Parkin ligate
ubiquitin to Parkinson’s disease? EMBO Rep 5, 681–
685.
72 Winklhofer KF, Henn IH, Kay-Jackson PC, Heller U
& Tatzelt J (2003) Inactivation of Parkin by oxidative
stress and C-terminal truncations: a protective role
of molecular chaperones. J Biol Chem 278, 47199–
47208.
73 Anderson JK (2004) Oxidative stress in neurodegenera-
tion: cause or consequence? Nat Rev Neurosci 10(Sup-
pl.), S18–S25.
74 Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi
K & Ariga H (2004) DJ-1 has a role in antioxidative
stress to prevent cell death. EMBO Rep 5, 213–218.
75 Martinat C, Shendelman S, Jonason A, Leete T, Beal
MF, Yang L, Floss T & Abeliovich A (2004) Sensitivity
to oxidative stress in DJ-1-deficient dopamine neurons:
an ES-derived cell model of primary parkinsonism.

drial import and enzymatic activity of PINK1 mutants
associated to recessive parkinsonism. Hum Mol Genet
14, 3477–3492.
82 Unoki M & Nakamura Y (2001) Growth-suppressive
effects of BPOZ and EGR2, two genes involved in
the PTEN signaling pathway. Oncogene 20, 4457–
4465.
83 Kim RH, Peters M, Jang Y, Shi W, Pintilie M, Fletcher
GC, DeLuca C, Liepa J, Zhou L, Snow B et al. (2005)
DJ-1, a novel regulator of the tumor suppressor PTEN.
Cancer Cell 7 , 263–273.
84 Fallon L, Be
´
langer CM, Corera AT, Kontogiannea M,
Regan-Klapisz E, Moreau F, Voortman J, Haber M,
Rouleau G, Thorarinsdottir T et al. (2006) A regulated
interaction with the UIM protein Eps15 implicates Par-
kin in EGF receptor trafficking and PI(3)K-Akt signal-
ling. Nat Cell Biol 8, 834–842.
85 Yang L, Sun M, Sun XM, Cheng GZ, Nicosia SV &
Cheng JQ (2007) Akt attenuation of the serine protease
activity of HtrA2 ⁄ Omi through phosphorylation of
serine 212. J Biol Chem 282, 10981–10987.
86 Yamamoto A, Friedlein A, Imai Y, Takahashi R, Kah-
le PJ & Haass C (2005) Parkin phosphorylation and
modulation of its E3 ubiquitin ligase activity. J Biol
Chem 280, 3390–3399.
87 Avraham E, Rott R, Liani E, Szargel R & Engelender
S (2007) Phosphorylation of Parkin by the cyclin-depen-
dent kinase 5 at the linker region modulates its ubiqu-

function affects development and results in neurodegen-
eration in zebrafish. J Neurosci 28, 8199–8207.
93 Falkenburger BH & Schulz JB (2006) Limitations of
cellular models in Parkinson’s disease research. J Neural
Transm 70 (Suppl.), 261–268.
94 Hyun-Park I, Arora N, Huo H, Maherali N, Ahfeldt T,
Shimamura A, Lensch MW, Cowan C, Hochedlinger K
& Daley GQ (2008) Disease-specific induced pluripotent
stem cells. Cell 134, 1–10.
95 Nishikawa S, Goldstein RA & Nierras CR (2008) The
promise of human induced pluripotent stem cells
for research and therapy. Nat Rev Mol Cell Biol 9,
725–729.
96 Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM,
Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel
R, Goland R et al. (2008) Induced pluripotent stem
cells generated from patients with ALS can be differen-
tiated into notor neurons. Science 321, 1218–1221.
Autosomal recessive genes in Parkinson’s disease J. C. Fitzgerald and H. Plun-Favreau
5766 FEBS Journal 275 (2008) 5758–5766 ª 2008 The Authors Journal compilation ª 2008 FEBS