1 sulting from mutations in GRN (which encodes
progranulin).
2 expression increases intracellular levels of
progranulin.
3 ntia: microtubule-associated protein tau and
progranulin.
4 in rat primary cortical neurons treated with
progranulin.
5 ytosis of amyloid beta1-42 when treated with
progranulin.
6 ases, is a functional signaling receptor for
progranulin.
7 All cause haploinsufficiency of
progranulin,
a protein involved in inflammation, tissue
8 t membranes and cell surfaces, we identified
progranulin,
a secreted growth factor, as a strong inter
9 s of function mutations in the gene encoding
progranulin,
a secreted growth factor.
10 he growth factor proepithelin (also known as
progranulin,
acrogranin, PC-derived growth factor, or gr
11 These data demonstrate that
progranulin acts as a chemoattractant in the brain to re
12 Moreover,
progranulin alone was sufficient to promote migration of
13 Adeno-associated virus-
progranulin also corrected lysosomal abnormalities in Gr
14 Notably, both
progranulin and domain V stimulated the growth of adrena
15 for such a receptor, providing insight into
progranulin and EphA2 signaling.
16 Progranulin and granulins are attributed with roles in c
17 <0.01), and MMP-13 (r = 0.788, P <0.01); and
progranulin and IL-8 (r = 0.762, P <0.01), MMP-8 (r = 0.
18 601 mRNAs were changed (including Fus (Tls),
progranulin and other transcripts encoding neurodegenera
19 nvestigated the molecular nature of secreted
progranulin and provide evidence that progranulin exists
20 The relationship between
progranulin and TDP-43 and their respective roles in neu
21 nvolving microtubule-associated protein tau,
progranulin and TDP-43, potential disease-modifying ther
22 ade in understanding the normal functions of
progranulin and TDP-43, the molecular interactions betwe
23 MAPT/tau, GRN/
progranulin,
and C9ORF72 have emerged as common FTD gene
24 RF72 from subjects with mutations in tau and
progranulin,
and from sporadic frontotemporal dementia.
25 causing impaired production or secretion of
progranulin are a common Mendelian cause of FTLD-TDP; ad
26 we identify and functionally characterize a
progranulin [
Biomphalaria glabrata granulin (BgGRN)] fro
27 These data support the concept of
progranulin-
boosting therapies for frontotemporal dement
28 Recombinant
progranulin bound with high affinity to EphA2 in both so
29 Cell surface receptors for
progranulin,
but not granulin peptides, have been report
30 Additionally, recombinant
progranulin can be intermolecularly cross-linked, yieldi
31 Furthermore, ECM1 and
progranulin chondrogenic growth factor constitute an int
32 ing to a dimer ( approximately 180 kDa), and
progranulins containing different epitope tags physicall
33 poral dementia and it is unclear if boosting
progranulin could correct pre-existing deficits.
34 Thus,
progranulin deficiency induced FTD-like behavioral and n
35 in global Grn+/- mice, showing that neuronal
progranulin deficiency is sufficient to disrupt social b
36 ficits and suggesting an important effect of
progranulin deficiency on neurons.
37 r, homozygous GRN mutations causing complete
progranulin deficiency were recently shown to cause a di
38 consequences, of neurodegeneration caused by
progranulin deficiency.
39 n of autofluorescent material was present in
Progranulin deficient mice at 12 months.
40 Retinas of both wild-type and
Progranulin deficient mice were examined by immunostaini
41 inal neurodegeneration as a new phenotype in
progranulin-
deficient FTLD, and suggest a pathological l
42 Both neuronal
progranulin-
deficient lines developed social dominance d
43 Eighteen-month-old
progranulin-
deficient mice demonstrated impaired spatial
44 In this study, we showed that
progranulin-
deficient mice displayed increased depressio
45 In addition to behavioral deficits,
progranulin-
deficient mice showed a progressive developm
46 -related deficits, we generated two neuronal
progranulin-
deficient mouse lines using CaMKII-Cre and N
47 Augmented expression of Ran in
progranulin-
deficient neurons restores nuclear TDP-43 le
48 We conclude that circulating
progranulin exists as a dimer and is not likely a compon
49 creted progranulin and provide evidence that
progranulin exists as a homodimer.
50 ulin haploinsufficiency, therefore, boosting
progranulin expression from the intact allele is a ratio
51 following findings: (1) confirmation of high
progranulin expression levels in peripheral blood; (2) t
52 ted (including in sortilin, the receptor for
progranulin)
following depletion of TDP-43 from mouse ad
53 PI may be due to protection of growth factor
progranulin from enzymatic cleavage or suppression of CR
54 Mutations in the
progranulin gene (GRN) are a major cause of frontotempor
55 Mutations in the
progranulin gene (GRN) are an important cause of frontot
56 Loss-of-function mutations in the
progranulin gene (GRN) cause frontotemporal lobar degene
57 Mutations in the
progranulin gene (GRN) causing impaired production or se
58 Mutations in the
progranulin gene (GRN) have recently been identified as
59 The
progranulin gene (GRN) is mutated in 5-10% of patients w
60 Mutations in the
progranulin gene (PGRN) have been shown to cause familia
61 Mutations in the
Progranulin gene (PGRN) recently have been discovered to
62 Null mutations in the
progranulin gene (PGRN) were recently reported to cause
63 been reported to carry null mutations in the
progranulin gene (PGRN).
64 Mutations in the
progranulin gene are a major cause of familial frontotem
65 Mutations in the
progranulin gene are known to cause diverse clinical syn
66 Complete loss of the
progranulin gene did not worsen TDP-43 toxicity, whereas
67 emporal lobar degeneration, mutations in the
progranulin gene may be a risk factor for AD clinical ph
68 We describe 2 patients with
progranulin gene mutations and evidence of Alzheimer dis
69 Mutations in the human
progranulin gene resulting in protein haploinsufficiency
70 Molecular pathways enriched in the
progranulin gene set included cell adhesion and cell mot
71 ygous loss-of-function mutations in GRN, the
progranulin gene, are a common genetic cause of the diso
72 with FTD, although until recently only two [
progranulin (
GRN) and microtubule-associated protein tau
73 Progranulin (
GRN) and TMEM106B are associated with sever
74 Loss-of-function mutations in
progranulin (
GRN) cause ubiquitin- and TAR DNA-binding p
75 Haploinsufficiency in the
progranulin (
GRN) gene accounts for 10% of all cases of
76 Mutations in the
progranulin (
GRN) gene are responsible for 20% of famili
77 Mutations in the
progranulin (
GRN) gene have recently been reported as a
78 subgroup analyses based on brain region and
progranulin (
GRN) gene status.
79 Progranulin (
GRN) haploinsufficiency is a frequent cause
80 Haploinsufficiency of
progranulin (
GRN) is a major genetic risk factor for fro
81 Recent studies suggest
progranulin (
GRN) is a neurotrophic factor.
82 ciency in frontotemporal dementia (FTD) gene
progranulin (
Grn) leads to an age-dependent, progressive
83 neration showed linkage to the region of the
progranulin (
GRN) locus and a homozygous mutation was de
84 Progranulin (
GRN) loss-of-function mutations leading to
85 l Lobar Degeneration (FTLD) known stems from
Progranulin (
GRN) mutation and exhibits TDP-43 plus ubiq
86 Progranulin (
GRN) mutations cause frontotemporal dementi
87 Progranulin (
GRN) mutations causing haploinsufficiency a
88 sk of FTLD-TDP was observed in patients with
progranulin (
GRN) mutations.
89 Loss-of-function mutations in
progranulin (
GRN), a secreted glycoprotein expressed by
90 tic mutations usually in one of three genes:
progranulin (
GRN), microtubule-associated protein tau (M
91 Mutations in the gene encoding
progranulin (
GRN), which lead to reduced progranulin lev
92 dochondral ossification via associating with
progranulin growth factor.
93 ate that FTD-related deficits resulting from
progranulin haploinsufficiency can develop in the absenc
94 Mutations resulting in
progranulin haploinsufficiency cause disease in patients
95 Progranulin haploinsufficiency causes frontotemporal dem
96 of the disorder, but the mechanisms by which
progranulin haploinsufficiency causes neuronal dysfuncti
97 ght to cause frontotemporal dementia through
progranulin haploinsufficiency, therefore, boosting prog
98 in heterozygous (Grn(+/-)) mice, which model
progranulin haploinsufficiency.
99 Although recombinant
progranulin has a molecular mass of approximately 85 kDa
100 Progranulin has also been implicated in cell growth, wou
101 gene did not worsen TDP-43 toxicity, whereas
progranulin heterozygosity did.
102 Here, we studied
progranulin heterozygous (Grn(+/-)) mice, which model pr
103 At 3 months, visfatin,
progranulin,
IL-8, and MMP-8 levels were significantly d
104 mutations and suggests a potential role for
progranulin in Alzheimer's disease.
105 Localized lentiviral expression of
progranulin in C57BL/6 mice resulted in an increase of I
106 derstanding the underlying mode of action of
progranulin in cancer progression, tumor angiogenesis, a
107 ndogenous neuronal TMEM106B colocalizes with
progranulin in late endo-lysosomes, and TMEM106B overexp
108 ghlight an important role for neuron-derived
progranulin in maintaining normal social function.
109 on chromatography, we found no evidence that
progranulin in mouse or human plasma is a component of H
110 xo4- and Stat3-dependent IL-10 production by
progranulin in regulatory T cells restrains inflammatory
111 ts uncover a previously unrecognized role of
progranulin in suppressing aberrant microglia activation
112 Moreover, a reduction in
progranulin in tau transgenic mice is associated with in
113 ration; however, the biological functions of
progranulin in the brain remain unknown.
114 To further test the role of neuronal
progranulin in the development of frontotemporal dementi
115 adeno-associated virus-driven expression of
progranulin in the medial prefrontal cortex reverses soc
116 We have characterized the normal function of
progranulin in the nematode Caenorhabditis elegans.
117 Visfatin, chemerin,
progranulin,
interleukin (IL)-1beta, IL-8, MMP-8, and MM
118 Progranulin is a secreted glycoprotein, and the GRN gene
119 Progranulin is a secreted protein with roles in tumorige
120 Progranulin is cleaved into smaller peptides called gran
121 the intracellular functions of granulins and
progranulin is crucial for understanding their contribut
122 els in these lines indicated that most brain
progranulin is derived from neurons.
123 Therefore, whether
progranulin is involved in recruitment of immune cells i
124 Although
progranulin is involved in wound healing, inflammation,
125 Progranulin is proteolytically processed into granulins,
126 neurons, suggesting that restoring neuronal
progranulin is sufficient to correct deficits in Grn+/-
127 Granulin (GRN, or
progranulin)
is a protein involved in wound repair, infl
128 Granulin-epithelin precursor (GEP/
progranulin)
is an autocrine growth factor for ovarian c
129 PC cell-derived growth factor, also known as
progranulin,
is an M(r) 88,000 growth factor (referred a
130 Homozygous
progranulin knock-out (Grn(-/-)) mice have been studied
131 ise, we found that macrophages cultured from
progranulin KO mice displayed enhanced rates of apoptoti
132 ipheral blood; (2) two subjects with reduced
progranulin levels and mutations in the PGRN gene confir
133 Measuring
progranulin levels in these lines indicated that most br
134 Although elevation of secreted
progranulin levels through a post-transcriptional mechan
135 ing progranulin (GRN), which lead to reduced
progranulin levels, are a significant cause of familial
136 inosis, suggesting that the total absence of
progranulin may have effects distinct from those of hapl
137 at abnormal metabolism of TDP-43 mediated by
progranulin may play a pivotal role in neurodegeneration
138 r than or in addition to loss of full-length
progranulin,
may contribute to disease in TDP-43 protein
139 The plasma
progranulin measurement, which is predictive of GRN muta
140 We report that
progranulin mediates proteolytic cleavage of TDP-43 to g
141 cover from damage or injury are destroyed in
progranulin mutants, which in turn facilitates disease p
142 ffered across subjects with C9ORF72, tau and
progranulin mutations and sporadic frontotemporal dement
143 on case reports of 2 unrelated patients with
progranulin mutations at the University of California, S
144 Progranulin mutations result in frontotemporal dementia,
145 vidual variation; however, within this group
progranulin mutations were associated with strongly asym
146 Progranulin mutations were identified as a major cause o
147 sion was significantly more symmetrical than
progranulin mutations with significantly less temporal l
148 mutations, 25 with tau mutations and 12 with
progranulin mutations) and 20 sporadic subjects with beh
149 temporoparietal atrophy was associated with
progranulin mutations.
150 clinical features in cases with and without
progranulin mutations.
151 ur groups: 1) familial FTD with mutations in
progranulin (
n = 36), valosin-containing protein (n = 5)
152 ported in subjects with mutations in tau and
progranulin,
no imaging features have been published in
153 overy of a functional signaling receptor for
progranulin offers a new avenue for understanding the un
154 Although
progranulin partially co-fractionated with high density
155 at white matter involvement may be linked to
progranulin pathological processes in a subset of GRN mu
156 expression of TMEM106B, which in turn alters
progranulin pathways.
157 Thus,
progranulin/
perlecan interaction could contribute to a f
158 Heterozygous mutations in
progranulin (
PGRN) cause familial FTD and result in decr
159 within the granulin (GRN) gene that encodes
progranulin (
PGRN) cause the neurodegenerative disease f
160 Haploinsufficiency of
progranulin (
PGRN) due to mutations in the granulin (GRN
161 Haploinsufficiency of the
progranulin (
PGRN) gene (GRN) causes familial frontotemp
162 ave been identified in familial cases in the
progranulin (
PGRN) gene, also on chromosome 17q21.
163 milial FTDP associated with mutations in the
progranulin (
PGRN) gene, particularly in those cases wit
164 the presence of mutations in tau (MAPT) and
progranulin (
PGRN) genes.
165 Progranulin (
PGRN) haploinsufficiency resulting from los
166 The growth factor
progranulin (
PGRN) has been implicated in embryonic deve
167 Loss-of-function mutations of
progranulin (
PGRN) have been linked to frontotemporal de
168 Progranulin (
PGRN) is a secreted glycoprotein expressed
169 Progranulin (
PGRN) is a widely expressed protein involve
170 Progranulin (
PGRN) is a widely expressed secreted protei
171 Progranulin (
PGRN) is involved in wound repair, inflamma
172 Progranulin (
PGRN) is known to have anti-inflammatory ac
173 We screened total-blood
progranulin (
PGRN) levels in 107 patients with neurodege
174 Progranulin (
PGRN) restrains inflammation and is therape
175 hese families, FTD is caused by mutations in
progranulin (
PGRN) that are likely to create null allele
176 Haploinsufficiency of
Progranulin (
PGRN), a gene encoding a secreted glycoprot
177 Sortilin 1 regulates the levels of brain
progranulin (
PGRN), a neurotrophic growth factor that, w
178 Progranulin (
PGRN), a pleiotrophic growth factor, is kno
179 Progranulin (
PGRN), a secreted growth factor, is a key r
180 By studying mice lacking
progranulin (
PGRN), the protein encoded by GRN, we disco
181 ients with GRN mutations and in mice lacking
progranulin (
PGRN).
182 (GRN) loss-of-function mutations leading to
progranulin protein (PGRN) haploinsufficiency are preval
183 egfa and Grn mRNAs and may ultimately affect
progranulin protein content, whereas FUS does not affect
184 To investigate the influence of a decline in
progranulin protein on other forms of neurodegenerative-
185 chanism that leads to the loss of functional
progranulin protein.
186 Our data suggest that
progranulin reduction might be the cause of multiple pro
187 In plasma,
progranulin similarly forms complexes of approximately 1
188 eneration, including TDP-43 itself, FUS/TLS,
progranulin,
Tau, and ataxin 1 and -2.
189 Within
progranulin,
the subdomains interacting most with perlec
190 first report of a small molecule enhancer of
progranulin transcription.
191 ut not inflammation were also increased from
progranulin-
treated primary neurons.
192 ress with mouse models based on tau, TDP-43,
progranulin,
VCP, and CHMP2B.
193 The adeno-associated virus-
progranulin vector only transduced neurons, suggesting t
194 Although the growth factor
progranulin was discovered more than two decades ago, th
195 Progranulin was present within proliferating blood vesse
196 ore, we found an autoregulatory mechanism of
progranulin whereby a feed-forward loop occurred in an E
197 Interaction of
progranulin with EphA2 caused prolonged activation of th
198 The interaction of
progranulin with perlecan domain V involved the first tw